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1.
Article in Chinese | WPRIM | ID: wpr-920556

ABSTRACT

@#Salivary exosomes are extracellular vesicles with a diameter of 30-50 nm in saliva. With the development of technology in recent years, many studies have revealed that salivary exosomes play an important role in the occurrence and development of various oral diseases. For example, salivary exosomal CD9 and CD81 promote tumor cell metastasis by regulating the cell adhesion and movement, salivary exosomal miR-24-3p promotes the tumor cell proliferation by acting on PER1, and salivary exosomal programmed cell death-ligand 1 (PD-L1) mRNA inhibits the destruction of inflammatory tissue, which can be biomarkers for the diagnosis of oral cancer, periodontitis and other oral diseases. Therefore, salivary exosomes can be used as potential prognostic and diagnostic markers for oral diseases. In addition to oral diseases, such as oral cancer, periodontitis, oral lichen planus, Sjogren’s syndrome, etc., salivary exosomes are closely related to distant tumors, such as pancreatic cancer, lung cancer, and systemic diseases, such as Parkinson’s disease, inflammatory bowel disease, etc. It is of great significance to study the role of salivary exosomes in the diagnosis and treatment of oral and systemic diseases and to develop the potential of salivary exosomes as biomarkers for disease diagnosis.

2.
Acta Pharmaceutica Sinica ; (12): 150-158, 2022.
Article in Chinese | WPRIM | ID: wpr-913181

ABSTRACT

Exosomes are one of the most important ways of cell-to-cell communication in living lives. They are involved in major physiological and pathological processes, including drug resistance, infection propagation, cancer development and cardiovascular diseases. The biological functions of exosomes made it possess characteristics of low immunogenicity, high delivery efficiency, ability to cross multiple biological barriers and targeting capacity, which also encourage people to try to use it as a drug carrier to overcome the disadvantages of poor stability, low solubility, low bioavailability and high toxicity of some drugs. In this paper, the latest progress of exosomes in the delivery of antitumor drugs, including small chemotherapeutic drugs, biological macromolecules and nucleic acid drugs, is reviewed. In addition, the isolation, drug loading, and modification method and the application prospect of exosomes are also discussed.

3.
Acta Pharmaceutica Sinica B ; (6): 1041-1053, 2022.
Article in English | WPRIM | ID: wpr-929344

ABSTRACT

The immune checkpoint blockade (ICB) targeting on PD-1/PD-L1 has shown remarkable promise in treating cancers. However, the low response rate and frequently observed severe side effects limit its broad benefits. It is partially due to less understanding of the biological regulation of PD-L1. Here, we systematically and comprehensively summarized the regulation of PD-L1 from nuclear chromatin reorganization to extracellular presentation. In PD-L1 and PD-L2 highly expressed cancer cells, a new TAD (topologically associating domain) (chr9: 5,400,000-5,600,000) around CD274 and CD273 was discovered, which includes a reported super-enhancer to drive synchronous transcription of PD-L1 and PD-L2. The re-shaped TAD allows transcription factors such as STAT3 and IRF1 recruit to PD-L1 locus in order to guide the expression of PD-L1. After transcription, the PD-L1 is tightly regulated by miRNAs and RNA-binding proteins via the long 3'UTR. At translational level, PD-L1 protein and its membrane presentation are tightly regulated by post-translational modification such as glycosylation and ubiquitination. In addition, PD-L1 can be secreted via exosome to systematically inhibit immune response. Therefore, fully dissecting the regulation of PD-L1/PD-L2 and thoroughly detecting PD-L1/PD-L2 as well as their regulatory networks will bring more insights in ICB and ICB-based combinational therapy.

4.
Acta Pharmaceutica Sinica B ; (6): 907-923, 2022.
Article in English | WPRIM | ID: wpr-929334

ABSTRACT

Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer, their inefficient therapeutic outcomes, serious adverse effects, and high cost of mass production remain crucial challenges. Herein, we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers (TFENs). These nanovehicles had desirable particle sizes (131 nm), exosome-like morphology, and negative zeta potentials. Furthermore, TFENs were found to contain large amounts of polyphenols, flavonoids, functional proteins, and lipids. Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species (ROS) amplification. The increased intracellular ROS amounts could not only trigger mitochondrial damage, but also arrest cell cycle, resulting in the in vitro anti-proliferation, anti-migration, and anti-invasion activities against breast cancer cells. Further mice investigations demonstrated that TFENs after intravenous (i.v.) injection or oral administration could accumulate in breast tumors and lung metastatic sites, inhibit the growth and metastasis of breast cancer, and modulate gut microbiota. This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v. and oral routes.

5.
Frontiers of Medicine ; (4): 157-175, 2022.
Article in English | WPRIM | ID: wpr-929191

ABSTRACT

Cancer imposes a severe threat to people's health and lives, thus pressing a huge medical and economic burden on individuals and communities. Therefore, early diagnosis of cancer is indispensable in the timely prevention and effective treatment for patients. Exosome has recently become an attractive cancer biomarker in noninvasive early diagnosis because of the unique physiology and pathology functions, which reflects remarkable information regarding the cancer microenvironment, and plays an important role in the occurrence and evolution of cancer. Meanwhile, biosensors have gained great attention for the detection of exosomes due to their superior properties, such as convenient operation, real-time readout, high sensitivity, and remarkable specificity, suggesting promising biomedical applications in the early diagnosis of cancer. In this review, the latest advances of biosensors regarding the assay of exosomes were summarized, and the superiorities of exosomes as markers for the early diagnosis of cancer were evaluated. Moreover, the recent challenges and further opportunities of developing effective biosensors for the early diagnosis of cancer were discussed.


Subject(s)
Biomarkers, Tumor , Biosensing Techniques , Early Detection of Cancer , Exosomes/pathology , Humans , Neoplasms/pathology , Tumor Microenvironment
6.
Chinese Journal of Lung Cancer ; (12): 351-357, 2022.
Article in Chinese | WPRIM | ID: wpr-928817

ABSTRACT

In China, malignant tumor is the main cause of death in both urban and rural areas. Mesenchymal stem cells (MSCs) have multidirectional differentiation potential, self-renewal ability and good immunomodulatory properties. Exosomes, as important paracrine substances of MSCs, mediate information exchange and transmission between cells in tumor microenvironment and influence the occurrence and development of tumors. Recently, conflicting findings have been reported on the effects of MSCs and their exosomes on tumors. On the one hand, MSCs and their exosomes are tumorigenic and can target specific sites to inhibit tumor growth; On the other hand, there is also evidence that MSCs could affect tumor growth and migration as part of the tumor microenvironment. In this paper, we will review the relationship between MSCs and exosomes and tumorgenesis and development, as well as how MSCs and exosomes play different roles in tumorgenesis and development, in order to provide beneficial help for tumor diagnosis, prognosis and precise treatment.
.


Subject(s)
Cell Differentiation , Exosomes , Humans , Lung Neoplasms , Mesenchymal Stem Cells , Tumor Microenvironment
7.
Article in Chinese | WPRIM | ID: wpr-928758

ABSTRACT

OBJECTIVE@#To investigate the changes of gene sequencing and proteomics of apheresis platelet (AP) exosomes in different storage periods and predict the function of AP exosomes in different storage periods.@*METHODS@#Platelets at different storage periods of 0 day (D0), 3 day (D3) and 5 day (D5) were collected, exosomes were extracted with Gradient centrifugation; gene sequencing and proteomic analysis were used to analyze the exosomes, and biological functions of platelet exosomes were analyzed and predicted by bioinformatics. Liquid mass spectrometry (LMS) was used to detect the changes and function prediction of exosomes proteins. The small RNA sequencing library was prepared, and the constructed library was sequenced and bioinformatics technology was used for data analysis.@*RESULTS@#AP exosome iTRAQ protein analysis showed that AP exosomes stored in D3 with 55 up-regulated proteins and 94 down-regulated proteins (P<0.05, FC<0.83 or FC>1.2), while AP exosomes stored in D5 with 292 up-regulated proteins and 53 down-regulated proteins (P<0.05, FC<0.83 or FC>1.2) as compared with D0. KEGG pathway analysis showed that the proteins were mainly involved in transport and metabolism, immune system, cancer, membrane transport and other processes. There were statistically significant differences between AP exosome miRNAs in different storage days (P<0.01). The number of miRNA up-regulated and down-regulated was 374 and 255 as compared with the number of platelet exosomes miRNA stored in D3 and D0, while that was 297 and 242 in D5 and D0, and 252 and 327 in D5 and D3, respectively. The target genes of differential platelet exosome miRNAs were analyzed by GO enrichment. Target genes of differential miRNA were mainly involved in membrane composition, mainly played molecular functions binding to proteins, and participated in biological processes of transcriptional regulation.@*CONCLUSION@#The exosome differential proteins and miRNAs in D5 are significantly different from those in the D0 of APs, and they are involved in various biological processes.


Subject(s)
Blood Component Removal , Blood Platelets/metabolism , Exosomes/metabolism , Humans , MicroRNAs/genetics , Proteomics
8.
Article in Chinese | WPRIM | ID: wpr-928620

ABSTRACT

OBJECTIVES@#To study the biological processes and functions of serum exosomes in children in the acute stage of Kawasaki disease (KD), so as to provide new biomarkers for the early diagnosis of KD.@*METHODS@#In this prospective study, 13 children with KD who were treated in Children's Hospital of Soochow University from June 2019 to August 2020 were enrolled as the KD group, and 13 children who were hospitalized due to bacterial infection during the same period were enrolled as the control group. Whole blood was collected on the next morning after admission, serum samples were obtained by centrifugation, and exosomes were extracted through ultracentrifugation. Serum exosomes were analyzed by label-free quantitative proteomics, and differentially expressed proteins (DEPs) were screened out for functional enrichment analysis. A protein-protein interaction (PPI) network was plotted, and unique proteins were validated by targeted proteomics.@*RESULTS@#A total of 131 DEPs were screened out for the two groups, among which 27 proteins were detected in both groups. There were 48 unique DEPs in the KD group, among which 23 were upregulated and 25 were downregulated, and these proteins acted on "complement and coagulation cascades" and "the MAPK signaling pathway". Validation by targeted proteomics showed that FGG, SERPING1, C1R, C1QA, IGHG4, and C1QC proteins were quantifiable in the KD group. A total of 29 proteins were only expressed in the control group, among which 12 were upregulated and 17 were downregulated. Four proteins were quantifiable based on targeted proteomics, i.e., VWF, ECM1, F13A1, and TTR. A PPI network was plotted for each group. In the KD group, FGG and C1QC had close interaction with other proteins, while in the control group, VWF had close interaction with other proteins.@*CONCLUSIONS@#The serum exosomes FGG and C1QC in children in the acute stage of KD are expected to become the biomarkers for the early diagnosis of KD. For children with unexplained fever, detection of FGG, C1QC1, and VWF may help with etiological screening.


Subject(s)
Biomarkers , Child , Exosomes , Extracellular Matrix Proteins , Humans , Mucocutaneous Lymph Node Syndrome/diagnosis , Prospective Studies , Proteomics , von Willebrand Factor
9.
Article in English | WPRIM | ID: wpr-928610

ABSTRACT

Neuroblastoma (NB) is the most common extracranial solid tumor in children and has the features of high recurrence rate and low survival rate, and therefore, early diagnosis, treatment response evaluation, and recurrence monitoring are of great significance for NB patients. Liquid biopsy refers to the detection of cells and nucleic acids in fluid specimens, mainly blood. It is noninvasive and can overcome tumor heterogeneity, thus making it possible to achieve the early diagnosis and dynamic detection of NB. This review introduces the latest advances in clinical research on the application of liquid biopsy in NB.


Subject(s)
Child , Humans , Liquid Biopsy , Neuroblastoma/diagnosis
10.
Acta Pharmaceutica Sinica ; (12): 658-669, 2022.
Article in Chinese | WPRIM | ID: wpr-922881

ABSTRACT

Brain-targeted delivery plays an important role in the diagnosis and treatment of neurological diseases, but the existence of blood brain barrier (BBB) limits the development of brain-targeted delivery. As cell-derived nanovesicles, exosomes can participate in the transportation of substances between cells to mediate the communication between cells to play a biological regulatory role in vivo. Due to the low immunogenicity, low toxicity, high engineering and natural crossing over BBB, exosomes play an important role in brain-targeted delivery. In this paper, the composition of exosomes, the mechanism of brain targeted delivery and its role in various brain diseases are systematically described.

11.
Acta Pharmaceutica Sinica ; (12): 627-637, 2022.
Article in Chinese | WPRIM | ID: wpr-922877

ABSTRACT

Exosomes are a kind of endosomal vesicles that are secreted by most if not all living cells. Due to their capability of delivering a variety of cargos, such as tissue- or cell-specific proteins, lipids, and genetic materials, and their broad biological activities, exosomes have gained substantial attention as emerging therapeutics. Exosomes derived from mesenchymal stem cells (MSCs) and dendritic cells (DCs) are two types of exosomes that are widely studied. Many preclinical and clinical studies have shown that they have a satisfactory treatment effect in lung diseases, liver diseases, nervous system diseases, tumors, and other diseases. In addition, exosomes from macrophages, tumor cells, plant cells, and many other cells are getting more attention due to their therapeutic potential. Besides natural exosomes, research on engineered exosomes has also made plenty of progress. There have been several engineering methods of exosomes, such as targeting modification and loading of active ingredients. In this review, we summarize the research progress of therapeutic exosomes from different sources, and further discusses the application prospects of exosomes and possible challenges in the future.

12.
São Paulo; s.n; s.n; 2022. 263 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1379332

ABSTRACT

Os ribossomos são complexos ribonucleoproteicos conservados formados por duas subunidades assimétricas (40S e 60S em eucariotos) responsáveis pela tradução da informação genética e catálise da síntese proteica. A montagem destes complexos em eucariotos é mais bem descrita em S. cerevisiae, constituindo um processo celular energeticamente dispendioso e com múltiplas etapas. Ela tem origem no nucléolo com a transcrição do pré-rRNA 35S e requer o recrutamento hierárquico e transiente de cerca de 200 fatores de montagem para garantir a formação correta dos centros funcionais aptos à tradução. Neste processo, que se estende no núcleo e citoplasma, 79 proteínas ribossomais associam-se gradativamente à medida que o prérRNA é dobrado, modificado e processado. O processamento do pré-rRNA 35S consiste na remoção progressiva de espaçadores internos (ITS1 e ITS2) e externos (5ETS e 3ETS), que separam e flanqueiam os rRNAs maduros componentes de ambas subunidades ribossomais. A clivagem do ITS1 separa as vias de maturação do pré-60S e do pré-40S. O ITS2, que, em associação a fatores de montagem, forma uma estrutura denominada ITS2-foot, é o último espaçador do pré-60S a ser removido. A composição do ITS2-foot permanece inalterada no nucléolo até a transição entre o estado E nucleolar e a formação da partícula Nog2 nuclear. Nesta etapa, a liberação do fator Erb1 permite o recrutamento do fator de montagem conservado e essencial Nop53. Na base do ITS2-foot, Nop53 recruta o exossomo via RNA helicase Mtr4 para a clivagem 3-5 exonucleolítica de parte do ITS2 levando à desmontagem do ITS2-foot. O fato de Nop53 atuar como ponte entre dois grandes complexos e apresentar uma estrutura flexível e estendida nos levou a aprofundar a caracterização de seu papel durante a maturação do pré60S. Neste trabalho, usando análise proteômica quantitativa label-free baseada em espectrometria de massas, caracterizou-se o interactoma de Nop53, e avaliou-se o impacto da depleção de Nop53 no interactoma da subunidade catalítica do exossomo Rrp6 e na composição de pré-ribossomos representativos de quase todas as etapas de maturação do pré-60S. Em paralelo, foram caracterizados mutantes truncados de Nop53 e avaliada por pull-down a interação de Nop53 com componentes do exossomo. Os resultados obtidos mostraram que Nop53 é capaz de interagir com o cofator do exossomo Mpp6, sugerindo pontos adicionais de interação durante o recrutamento do exossomo ao pré-60S. A análise do interactoma de Rrp6 mostrou uma associação precoce do exossomo aos intermediários pré-ribossomais nucleolares mais iniciais, anteriores aos previamente descritos. Mudanças na composição dos intermediários pré-60S revelaram que a depleção de Nop53 afeta a transição entre o estado E e a partícula Nog2, afetando eventos tardios de maturação como o recrutamento de Yvh1. Comparando-se o efeito da depleção de Nop53 com o de mutantes nop53 desprovidos da região de recrutamento do exossomo, obtivemos evidências bioquímicas do papel estrutural de Nop53 na base do ITS2- foot. Em conjunto, estas observações, à luz de estruturas de intermediários pré-ribossomais recentemente descritas, nos permitiram concluir que o recrutamento de Nop53 ao pré-60S contribui para a estabilização de eventos de remodelamento do rRNA que antecedem a formação da partícula Nog2


Ribosomes are conserved ribonucleoprotein complexes formed by two asymmetric subunits (the 40S and the 60S in eukaryotes) responsible for translating the genetic information and catalyzing protein synthesis. The assembly of these complexes in eukaryotes is best described in S. cerevisiae. It is an energetically demanding, multi-step cellular process, that starts in the nucleolus with the transcription of the 35S pre-rRNA. It requires the hierarchical and transient recruitment of about 200 assembly factors to ensure the correct formation of the functional centers suitable for translation. In this process, which extends into the nucleus and cytoplasm, 79 ribosomal proteins gradually associate as the pre-rRNA is folded, modified, and processed. The 35S pre-rRNA processing happens with the progressive removal of internal (ITS1 and ITS2) and external (5'ETS and 3'ETS) transcribed spacers, which separate and flank the mature rRNA components of both ribosomal subunits. The cleavage at the ITS1 separates the pre-60S and pre40S maturation pathways. The ITS2, which in association with assembly factors constitutes a structure called ITS2-foot, is the last pre-60S spacer to be removed. The composition of the ITS2- foot remains unchanged in the nucleolus until the transition between the nucleolar state E and the nuclear Nog2 particle. At this stage, the release of Erb1 allows the recruitment of the conserved and essential assembly factor Nop53. At the base of the ITS2-foot, Nop53 recruits the exosome via the RNA helicase Mtr4 for the ITS2 3'-5' exonucleolytic cleavage leading to the ITS2-foot disassembly. The fact that Nop53 acts as a bridge between these two large complexes and exhibits a flexible and extended structure led us to further characterize its role in the pre-60S maturation. In this work, using mass spectrometry-based label-free quantitative proteomics, we characterized the interactome of Nop53, as well as the impact of the depletion of Nop53 on the interactome of the exosome catalytic subunit Rrp6 and on the composition of pre-ribosomes representative of almost all pre-60S maturation stages. In parallel, we characterized nop53 truncated mutants and evaluated the interaction of Nop53 with exosome components by pulldown assays. The results showed that Nop53 can interact with the exosome cofactor Mpp6, suggesting the contribution of additional points of interaction during the exosome recruitment to the pre-60S. The analysis of the Rrp6 interactome revealed an early association of the exosome with pre-ribosomal intermediates at very early nucleolar stages, before those previously described. Changes in the composition of pre-60S intermediates revealed that Nop53 depletion affects the transition between the state E and the Nog2 particle, affecting late pre-60S maturation events, such as the Yvh1 recruitment. Comparing the effect of Nop53 depletion with that of nop53 mutants lacking the exosome interacting region, we obtained biochemical evidence of the structural role of Nop53 at the base of the ITS2-foot. Altogether, and in light of recently described structures of pre-ribosomal intermediates, these observations allowed us to conclude that the recruitment of Nop53 to the pre-60S contributes to the stabilization of rRNA remodeling events that precede the formation of the Nog2 particle


Subject(s)
Saccharomyces cerevisiae/classification , Ribosome Subunits/chemistry , Ribonucleoproteins , Ribosomal Proteins , Mass Spectrometry/methods , Cell Nucleolus , Ribosome Subunits, Large , Eukaryota
13.
Acta Pharmaceutica Sinica ; (12): 778-785, 2021.
Article in Chinese | WPRIM | ID: wpr-876510

ABSTRACT

This study investigated the mechanism by which icaritin (ICT) inhibits exosomes-induced lung metastasis of B16BL6 mouse melanoma cells. The culture supernatant of B16BL6 cells was collected for extraction of exosomes by ultracentrifugation and their characterization by transmission electron microscopy and Western blotting. Exosomal protein was quantified by BCA. A wound-healing assay was used to determine the effect of ICT on the migratory ability of B16BL6 cells induced by exosomes. After establishing an experimental melanoma lung metastasis model in C57BL/6 mice, we used H&E staining to study the ability of ICT to inhibit exosomes-induced melanoma metastasis. Animal experiments were approved by the Ethics Committee of Nanjing University of Chinese Medicine. ELISA and immunofluorescence were used to detect pro-inflammatory factors interleukin 6 (IL-6), S100 calcium-binding protein A8/A9 complex (S100A8/A9), serum amyloid A (SAA) and fibronectin in metastatic tumors. The expression of metastatic tissue-related proteins stimulator of interferon gene (STING), phospho-STING (p-STING), TANK-binding kinase 1 (TBK1) and phospho-TBK1 (p-TBK1) was detected by immunohistochemistry or Western blotting. The results showed that the particle size of exosomes was 149.33 ± 2.68 nm, the polydispersity index (PDI) was 0.192 ± 0.02, the zeta potential was -32.22 ± 0.50 mV, and the particles had classic tea tray-like membrane structure under TEM. The protein concentration of exosomes was measured to be 838.66 ± 62.14 μg·mL-1. The results of the cell scratch test showed that ICT can inhibit exosomes-induced migration of B16BL6 cells at a concentration of 5, 10, and 20 μmol·L-1. In vivo experimental results also showed that ICT can inhibit exosomes-induced metastasis of melanoma to the lungs and can significantly inhibit the expression of pro-inflammatory factors S100A8/A9, SAA and IL-6 in lung tissue, and inhibit the expression of p-STING and p-TBK1 in metastatic lung tissue. Taken together, these results indicated that ICT can significantly inhibit exosomes-induced tumor metastasis, and the inhibition is related to the inactivation of STING in metastatic foci.

14.
Article in Chinese | WPRIM | ID: wpr-876115

ABSTRACT

@#[Abstract] Objective: To explore the effect of exosome-derived miR-181a on angiogenesis and tumor progression in gliomas. Methods: 83 cases of glioma tissues and 13 cases of peritumoral tissues resected in the Second Affiliated Hospital of Hainan Medical University from August 2017 to December 2019, glioma cells U87, A172, U251, LN229, U373 and microglial cell line HM, were selected to detect the expression of miR-181a in tumor tissues and cells by qPCR method. Glioma U373 cells with miR-181a over-expression or knockdown were constructed, and exosomes were isolated and identified. The effects of exsome-derived miR-181a on angiogenesis of HUVEC cells were investigated by tubule formation and chicken chorioallantoic membrane assay in vitro. Nude mice bearing U373 cell transplanted xenograft was constructed to observe the effect of exsome-derived miR-181a on angiogenesis and tumor growth in vivo. Results: The expression of miR-181a in glioma tissues and cells was significantly higher than that in normal tissues and normal glial HM cells (all P<0.01). The exsome-derived miR-181a could significantly promote the tubule formation of HUVEC cells (P<0.01) and the angiogenesis of chicken chorioallantoic membrane (all P<0.01). In vivo experiments showed that the growth of xenografts was promoted (P<0.05) and the amount of angiogenesis in the tumor tissues was increased in the nude mice after being transfused with exsome-derived miR-181a (P<0.01). Conclusion: miR-181a plays an important role in promoting angiogenesis of gliomas and may be a potential target for diagnosis and treatment of gliomas.

15.
Article in Chinese | WPRIM | ID: wpr-875834

ABSTRACT

@#[Abstract] Objective: To explore whether PDGF-BB can be transmitted through exosome and verify its angiogenic function in human osteosarcoma. Methods: Exosomes from a variety of human osteosarcoma cells were isolated. The expression of PDGF-BB in cells and exosomes was detected by WB. Exosomes derived from osteosarcoma SJSA-1 cells were co-incubated with HUVEC, and the pattern of exosomal PDGF-BB entering HUVEC was observed using Immunofluorescence and confocal scanning microscope. SJSA-1 cell lines with PDGF-BB over-expression or knockdown were constructed by lentiviral infection, and the exosomes derived from transfected SJSA-1 cells were isolated and incubated with HUVEC. Microtubule formation experiment was conducted to detect their effects on angiogenesis; SJSA-1 cell transplanted xenograft model was established in nude mice, and the exosomes derived from SJSA-1 cells with PDGF-BB over-expression or knockdown were infused into nude mice to observe their effects on tumor growth. Results: The exosomes derived from osteosarcoma cells were successfully isolated, in which a large amount of PDGF-BB was confirmed. The exosomes entered HUVEC by endocytosis. The SJSA-1 cell lines with PDGF-BB over-expression or knockdown were successfully constructed, and the corresponding exosomes were isolated. Compared with the control group, exosomes with high PDGF-BB content significantly promoted HUVEC angiogenesis (P < 0.01 , t=13.51) and tumor growth (P < 0.01 ), while exosomes with low PDGF-BB content reduced the angiogenesis ability of HUVEC (P < 0.01 , t=8.226) and inhibited tumor growth (P < 0.01 ). Conclusion: The exosomal PDGF-BB secreted by osteosarcoma cells can be directly absorbed by HUVEC and induce tumor angiogenesis, further promoting the growth of osteosarcoma.

16.
Article in English | WPRIM | ID: wpr-880742

ABSTRACT

Exosomes are nanometer-sized vesicles that contain various types of biologically active components, including proteins, nucleic acids, carbohydrates, and lipids, which vary with the type and physiological state of the cell. In recent years, several studies have showed that exosomes can provide new non-invasive diagnostic and prognostic biomarkers in patients affected by cancers, including bladder cancer (BC), and the lipid bilayer membrane structure makes exosomes as promising delivery vehicles for therapeutic applications. Exosomes have the characteristics of high abundance, high stability, tissue specificity, and wide distribution in body fluids, and are secreted as various types by cells in different states, thereby possessing great potential as biomarkers for BC. Herein, we briefly summarize the functions and roles of exosomes in the occurrence and development of BC and the current progress of research on exosomes in BC, while focusing on potential clinical applications of the diagnosis, treatment, and prognosis of BC.

17.
Chinese Journal of Hepatology ; (12): 1132-1136, 2021.
Article in Chinese | WPRIM | ID: wpr-922702

ABSTRACT

Hepatic fibrogenesis (HF) is the common consequence of various chronic liver diseases (CLD) induced by a variety of pathogenic factors. The mechanism of HF involves the interactions within different types of liver cells, cytokines, chemokines, cell mediators and multiple signaling pathways in a way of networks. As a result, excessive production and deposition of extracellular matrix (ECM) mainly composed of type I and type III fibril forming collagen destroys the original morphology, structure and function of the liver. The activation of hepatic stellate cells (HSCs), the major scar forming cells in liver, plays a crucial role in hepatic fibrogenesis. MicroRNAs are a group of short, single stranded, non-coding RNAs that can inhibit mRNA expression at the transcriptional and post transcriptional levels. They can be loaded and transferred as cargos by exosomes, to regulate the function of nearby and distant receptive cells. The expressions of many microRNAs such as miR-21, miR-29, miR-708, miR-101, miR-455, miR-146, miR-193 change significantly in activated HSCs, which regulate the activation, fibrogenic function, proliferation, apoptosis and autophagy of HSCs via affecting target genes expression and signaling pathway molecules. They are important substances and regulatory mechanism that mediate the initiation and progression of HF.


Subject(s)
Cell Proliferation , Gene Expression Regulation , Hepatic Stellate Cells , Humans , Liver Cirrhosis/pathology , MicroRNAs/genetics
18.
Article in Chinese | WPRIM | ID: wpr-908614

ABSTRACT

Objective:To explore the therapeutic effects of intravenous injection of small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (MSCs) on experimental autoimmune uveitis (EAU) in mice.Methods:MSCs from human umbilical cord were cultured and the supernatant was collected.The sEVs were isolated by ultracentrifugation method and a NanoSight instrument was used to analyze the particle size.The expression of surface markers sEVs, CD9, CD81 and CD63 was determined via Western blot.The morphology of sEVs was observed with a transmission electron microscope.Forty-eight 7-week-old female C57BL/6 mice were seclected to establish the EAU model through immunization with interphotoreceptor retinoid-binding protein peptide 651-670 (IRBP 651-670). The mice were divided into sEVs treatment group and phosphate buffer solution (PBS) control group using a random number table, with 24 mice in each group.The mice in the sEVs treatment group were injected with 50 μg of MSCs-derived sEVs via tail vein on the 11th day after modeling.In the PBS control group, the mice were injected with the same volume of PBS.Six mice in each group were randomly selected to observe the inflammation of the retina after mydriasis with an ophthalmoscope every other day from 8th day following modeling and the inflammation scores were evaluated.Six mice were randomly selected and sacrificed on the 14th day and 6 on the 18th day following modeling in each group, and both eyeballs of the mice were enucleated.Retinal tissue sections of the 6 mice sacrificed on the 18th day were stained with hematoxylin-eosin and the pathological scores were evaluated.The infiltration of helper T 1 (Th1) cells and Th17 cells in the eyeballs of the 6 mice sacrificed on the 18th day following modeling was detected by flow cytometry.T cells were isolated from spleen and lymph nodes of the 6 mice sacrificed on the 14th day, and the proliferation of T cells under different concentrations of IRBP 651-670 (0, 1, 10 and 20 μg/ml) was detected using a 5-bromodeoxyuridine (BrdU) method.To further study the effects of MSCs-derived sEVs on Th1/Th17 cells differentiation, naive T cells of spleen from another 3 normal mice were isolated by magnetic bead negative sorting and incubated with 10 μg/ml MSCs-derived sEVs or 10 μg/ml PBS, and then were cultured under Th1/Th17 cell differentiation conditions, respectively.Flow cytometry was used to measure the differentiation of naive T cells into Th1/Th17 cells.This study protocol complied with the regulations of the care and use of laboratory animals in China and was approved by an Ethics Committee of Tianjin Medical University (No.TJYY2019103022). Results:The isolated human MSCs-derived sEVs was with an average diameter of (102.4±33.6) nm and showed a double-layer membrane vesicle structure under the transmission electron microscope.The CD9, CD63 and CD81 proteins were highly expressed in sEVs.The inflammation scores of the sEVs treatment group were significantly lower than those in the control group on day 14, 16, 18, 20 and 22 after modeling (all at P<0.05). The pathological score of mice in the sEVs treatment group was significantly lower than that of PBS control group on the 18th day following modeling ( P<0.05). The flow cytometry results showed that on day 18 after modeling, the proportions of Th1 and Th17 cells in eyeballs in the sEVs treatment group were (15.55±2.03)% and (15.67±2.15)%, respectively, which were significantly lower than (21.35±0.72)% and (20.90±1.10)% in the PBS control group ( t=6.58, 5.31; both at P<0.01). BrdU results showed that when the IRBP 651-670 concentration was 20 μg/ml, the T cell proliferation ability in the sEVs treatment group was inhibited obviously compared with the control group ( P<0.05). The proportions of naive T cells differentiated into Th1 cells and Th17 cells in the sEVs treatment group were (28.15±1.32)% and (11.60±2.23)% respectively, which were significantly lower than (31.58±1.75)% and (23.52±1.76)% of the PBS control group, and the differences were statistically significant ( t=3.93, 10.26; both at P<0.05). Conclusions:Intravenous injection of human umbilical cord MSCs-derived sEVs can reduce the inflammation in EAU mice.The mechanism may be related to inhibiting the differentiation of naive T cells to Th1 and Th17 cells, and reducing the infiltration of Th1 and Th17 cells in the eyeballs.

19.
Article in Chinese | WPRIM | ID: wpr-907274

ABSTRACT

Mycobacterium tuberculosis(Mtb)is an intracellular bacteria that lives in the phagocytosis of host macrophages.After it invades the human body, it can cause a series of immune responses.Part of Mtb can be eliminated by the body′s immune function; some of them can survive by the immune escape mechanism and cause latent tuberculosis infection(LTBI)or tuberculosis(TB). Exosomes are extracellular vesicles with a diameter of 30-100 nm that are secreted by living cells.They are rich in proteins, lipids and nucleic acids, and exist in many body fluids of the human body.During Mtb infection, the components of exosomes released by the body can change significantly, and they can play an important role in the body′s infection and immune response, providing new ideas and theoretical basis for the prevention, diagnosis and treatment of tuberculosis infection.This article reviews the role and application value of exosomes in Mtb infection.

20.
Article in Chinese | WPRIM | ID: wpr-907255

ABSTRACT

Urine-derived stem cell(USC) refers to a type of mesenchymal stem cell obtained from urine.Due to its simple and quick extraction, non-invasive access, and no ethical issues, it has many advantages over other stem cells in clinical research, and has attracted the attention of the academic community.This article summarizes recent research progress in the aspects of urine-derived stem cell isolation and culture, cell characterizations, source, application, and exosomes.

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