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1.
Braz. j. biol ; 84: e250556, 2024. ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1360208

RESUMO

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.


Assuntos
Animais , Camundongos , Exossomos , Microambiente Tumoral , Sistema Imunitário , Metástase Neoplásica , Neoplasias
2.
FASEB J ; 37(3): e22733, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36723877

RESUMO

Accumulating evidence suggests that human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSCs-Exos) are a promising therapeutic strategy for cerebral ischemia-reperfusion injury (CIRI). However, the underlying mechanism remains unclear. hUC-MSCs-Exos were identified by electron microscopy, NTA, and Western blotting. In the hypoxia/reoxygenation (H/R) cell model, human brain microvascular endothelial cells (HBMECs) were cocultured with hUC-MSCs-Exos. Then, cell viability, migration, apoptosis, and tube formation were measured by MTT, flow cytometry, transwell, and tube formation assays. RT-qPCR and Western blotting were used to detect the changes in RNA and protein. RNA pull-down and dual luciferase reporter assays confirmed the relationship between circDLGAP4, miR-320, and KLF5. Ischemia-reperfusion (I/R) rat model was established for in vivo experiments. hUC-MSCs-Exos increased the expression levels of circDLGAP4 and KLF5 but decreased miR-320 in H/R-treated HBMECs by transferring exosomal circDLGAP4. Knockdown of circDLGAP4 in hUC-MSCs-Exos reversed the promoting effects of hUC-MSCs-Exos on cell viability, migration, and tube formation in H/R-treated HBMECs in vitro and also abolished the protective effects of hUC-MSCs-Exos on cerebrovascular injury in I/R rats. Mechanistically, exosomal circDLGAP4 negatively regulated miR-320 in HBMECs, which directly bound to KLF5. In addition, the downregulation of miR-320 could reverse the regulatory effect of exosomal shcircDLGAL5 in H/R-treated HBMECs by upregulating KLF5. hUC-MSCs-Exos-derived circDLGAP4 reduced cerebrovascular injury by regulating miR-320/KLF5 signaling. These results provide a stem cell-based approach to treat CIRI.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Traumatismo por Reperfusão , Humanos , Ratos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Células Endoteliais/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical/metabolismo , Exossomos/genética , Exossomos/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo
3.
J Immunol Res ; 2023: 8727884, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36726489

RESUMO

Background: The exosome is of vital importance throughout the entire progression of cancer. Because of the lack of effective biomarkers in ovarian cancer (OV), we intend to investigate the connection between exosomes and tumor immune microenvironment to verify that exosome-related genes (ERGs) can precisely forecast the prognosis of OV patients. Methods: First, 117 ERGs in The Cancer Genome Atlas (TCGA) dataset were recognized. Afterwards, the risk signature consisting of four ERGs with prognostic significance was built by univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis. We also validated the risk signature by Kaplan-Meier analysis, receiver operating characteristic curve analysis and principal component analysis. Furthermore, gene set enrichment analysis was performed to compare the enrichment patterns between the two risk subgroups. The connections between the exosome-related gene risk score (ERGRS) and clinical features, immune infiltration, immune checkpoint-related genes, copy number variation, and drug sensitivity were explored. We also assessed the function of the ERGRS to forecast immunotherapeutic efficacy by immunophenoscore (IPS). Results: The high-risk group had a worse prognosis than the group with low risk. We verified that the established model possessed a relatively good prognostic value. Pathway enrichment analysis indicated that the genome-wide group with low risk was enriched in immune-related pathways. We discovered that resting dendritic cells and stromal scores were upregulated in patients with high risk in the TCGA and Gene Expression Omnibus (GEO) cohorts. Moreover, the expression of six common immune checkpoint inhibitor targets was assessed, which revealed that the expression levels of CD274 (PD-L1), PDCD1 (PD-1), and IDO1 in patients with high risk were lower than those in patients with low risk. Afterwards, the low-risk group had higher IPS across the four immunotherapies, implying that it had better effects of immunotherapies. Conclusion: Our study demonstrates that the exosome-related gene risk model is closely associated with immune infiltration. It can well forecast the prognosis of OV patients and guide the selection of immunotherapeutic strategies.


Assuntos
Exossomos , Neoplasias Ovarianas , Humanos , Feminino , Variações do Número de Cópias de DNA , Exossomos/genética , Prognóstico , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Fatores de Risco , Microambiente Tumoral/genética
4.
Invest Ophthalmol Vis Sci ; 64(1): 9, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36648415

RESUMO

Purpose: Pathologic myopia (PM) is one of the primary causes of blindness. This study aims to explore the possible relations between the composition of microRNA in vitreous exosomes of patients with PM and the progression of myopic maculopathy. Methods: Vitreous humor (VH) samples were collected from patients undergoing retinal surgery. A total of 15 and 12 VH samples were obtained from patients with PM and control, respectively. The PM group was divided into PM-L (G2) and PM-H groups (G3 and G4) in order to explore differentially expressed microRNAs (DEMs) that account for the relatively poor prognosis in G3 and G4 myopic maculopathy. A Weighted Gene Co-Expression Network Analysis (WGCNA) was conducted to find the persistently altered key microRNAs in myopic maculopathy progression. The Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis were used. Results: High purity exosomes were extracted from the vitreous fluid of patients with PM and control. The top five downregulated DEMs of PM-H versus PM-L can reflect the tendency of deterioration of PM-H myopic maculopathy. MiR-143-3p and miR-145-5p, which were found in WGCNA, may participate in the development of myopic maculopathy. These microRNAs all relate to the insulin resistance pathway. Conclusions: This is the first study to explore the relations between the progression of myopic maculopathy and vitreous exosomal microRNAs. Vitreous exosomal miR-143-3p and miR-145-5p can be considered biomarkers for patients with PM, and the vitreous exosomal DEM associated with PM-H may represent alarming signals of myopic maculopathy deterioration.


Assuntos
Líquidos Corporais , Exossomos , Degeneração Macular , MicroRNAs , Miopia Degenerativa , Doenças Retinianas , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Miopia Degenerativa/genética , Corpo Vítreo/metabolismo , Exossomos/genética , Exossomos/metabolismo
5.
Skin Res Technol ; 29(1): e13259, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36704890

RESUMO

BACKGROUND: Targeting CD20+ melanoma cancer stem cells (CSCs) subset is essential for treating melanoma. Anti-CD20 aptamer-modified exosomes (ACEXO) loaded with Adriamycin could be a therapeutic strategy for targeting CSCs. MATERIALS AND METHODS: Exosomes loaded with Adriamycin were modified with anti-CD20 aptamer and characterized by size and molecular markers using transmission electron microscope and dynamic light scattering. The uptake of ACEXO into CD20+ cells was checked, and its cytotoxicities in CD20+ melanoma cells, HEK 293T, and 3T3 cells were evaluated. At the same time, the in vivo distribution of ACEXO in the tumor-bearing mice model was determined. RESULTS: The particle size of the exosome is about 80-100 nm. Western blot analysis showed that they expressed the characteristic exosome markers: CD9 and CD63. Quantitative analysis of the mean fluorescence intensity after 4 h incubation showed that ACEXO significantly improved Adriamycin uptake. Notably, the ACEXO killed only CD20+ melanoma cells. In addition, they exhibited good biocompatibility with both 293T and 3T3 cells at all doses. After intravenous injection, exosome distribution data showed that ACEXO's accumulation in the tumor is higher than anti-CD20-modified exosomes (AEXO)'s at all time points, and the accumulation increased as time prolonged. Addition of ACEXO reduces the number of tumorspheres in A375 or WM266-4 cells compared to untreated controls or AEXO-treated group. More important, while treating melanoma tumor-bearing mice, ACEXO-treated group showed the lowest tumor weight without body weight loss. CONCLUSION: ACEXO loaded with Adriamycin could suppress tumor cell growth in vitro and in vivo, probably by targeting CD20+ melanoma CSCs.


Assuntos
Exossomos , Melanoma , Humanos , Animais , Camundongos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Exossomos/patologia , Melanoma/tratamento farmacológico , Melanoma/patologia , Células-Tronco/patologia
6.
Cardiovasc Toxicol ; 23(1): 23-31, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36609664

RESUMO

Doxorubicin (Dox) is an anticancer drug widely used in tumor chemotherapy, but it has the side-effect of cardiotoxicity, which is closely related to mitochondrial damage. Mitochondrial dynamics is a quality control mechanism that usually helps to maintain a healthy mitochondrial pool. Trophoblast stem cell-derived exosomes (TSC-Exos) have been shown to protect cardiomyocytes from DOX-induced cardiotoxicity. To explore whether the cardioprotective role is mediated by the regulation of mitochondrial dynamic mechanism, TSC-Exos were isolated from human trophoblast stem cells by ultracentrifugation and characterized by Western blot and transmission electron microscopy. Cellular experiments of H9c2 cardiomyocytes co-cultured with Dox and TSC-Exos were performed in vitro to determine the levels of reactive oxygen species generation and apoptosis level. An animal model of heart failure was established by intraperitoneal injection of Dox in vivo, therapy mice were received additional intracardiac injection of TSC-Exos, then, the cardiac function, cardiomyocyte apoptosis and mitochondrial fragmentation were ameliorated. Histology assays suggest that Dox caused an increased tendency of mitochondrial fission, which was manifested by a decrease in the average size of mitochondria. By receiving TSC-Exos treatment, this effect was eliminated. In summary, these results suggest that TSC-Exos alleviate DOX-induced cardiotoxicity through antiapoptotic effect and improving mitochondrial fusion with an increase in Mfn2 expression. This study is the first to provide a potential new treatment scheme for the treatment of heart failure from the perspective of the relationship between TSC-Exos and mitochondrial dynamics.


Assuntos
Exossomos , Insuficiência Cardíaca , Camundongos , Animais , Humanos , Cardiotoxicidade/metabolismo , Dinâmica Mitocondrial , Exossomos/metabolismo , Trofoblastos/metabolismo , Doxorrubicina/toxicidade , Apoptose , Insuficiência Cardíaca/metabolismo , Células-Tronco/metabolismo , Miócitos Cardíacos , Estresse Oxidativo , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo
7.
Curr Opin Psychiatry ; 36(2): 119-125, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36705010

RESUMO

PURPOSE OF REVIEW: Dementia is a syndrome with several possible pathologies. To date, definitive methods for diagnosis and treatment of sub-types of dementia have not been established. Emerging evidence suggests that exosomes can provide important information for the diagnosis and treatment of several subtypes of dementia. This article reviews recent studies on the application of exosomes in dementia. RECENT FINDINGS: Exosomes are involved in the pathogenesis of Alzheimer's disease (AD) and Parkinson's disease (PD) through transporting toxic proteins such as amyloid beta (Aß), tau, and α-synuclein. Exosomal microRNAs (miR) and proteins reflect the disease state, and therefore, exosomes can be used as diagnostic markers for diseases such as AD, PD, Huntington's disease (HD), vascular dementia (VaD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Mesenchymal stem cell (MSC)-derived exosomes have been shown to ameliorate disease pathology, and improve cognitive function in AD, PD, and VAD. SUMMARY: Recent studies have shown that exosomes could be novel diagnostic agents for dementia because they contain molecules that could be potential biomarker candidates indicative of the type and stage of dementia. Therapeutic application of exosomes in dementia has revealed that exosomes only, or exosomes loaded with an active pharmaceutical ingredient (API), ameliorate disease phenotype of dementia. Further work is needed to exploit this potential.


Assuntos
Doença de Alzheimer , Exossomos , Doença por Corpos de Lewy , Doença de Parkinson , Humanos , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/terapia , Doença por Corpos de Lewy/metabolismo , Peptídeos beta-Amiloides/metabolismo , Exossomos/metabolismo , Exossomos/patologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/terapia , Doença de Alzheimer/metabolismo , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapia , Doença de Parkinson/metabolismo , Proteínas tau/metabolismo , Biomarcadores/metabolismo
8.
Zhonghua Zhong Liu Za Zhi ; 45(1): 50-55, 2023 Jan 23.
Artigo em Chinês | MEDLINE | ID: mdl-36709120

RESUMO

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.


Assuntos
Carcinoma Ductal Pancreático , Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Neoplasias Pancreáticas , Camundongos , Animais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Exossomos/genética , Sincalida/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/genética , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical
9.
Anal Chem ; 95(4): 2487-2495, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36683335

RESUMO

Exosomes are receiving highlighted attention as new biomarkers for the detection of cancer since they are profusely released by tumor cells in different biological fluids. In this paper, the exosomes are preconcentrated from the serum by immunomagnetic separation (IMS) based on a CD326 receptor as a specific epithelial cancer-related biomarker and detected by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcripts. Following the lysis of the captured exosomes, the released GAPDH transcripts are amplified by reverse transcription polymerase chain reaction (RT-PCR) with a double-tagging set of primers on poly(dT)-modified-MPs to increase the sensitivity. The double-tagged amplicon is then quantified by electrochemical genosensing. The IMS/double-tagging RT-PCR/electrochemical genosensing approach is first demonstrated for the sensitive detection of exosomes derived from MCF7 breast cancer cells and compared with CTCs in terms of the analytical performance, showing an LOD of 4 × 102 exosomes µL-1. The genosensor was applied to human samples by immunocapturing the exosomes directly from serum from breast cancer patients and showed a higher electrochemical signal (3.3-fold, p < 0.05), when compared with healthy controls, suggesting an overexpression of GAPDH on serum-derived exosomes from breast cancer patients. The detection of GAPDH transcripts is performed from only 1.0 mL of human serum using specific magnetic particles, improving the analytical simplification and avoiding ultracentrifugation steps, demonstrating to be a promising strategy for minimal invasive liquid biopsy.


Assuntos
Neoplasias da Mama , Exossomos , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Exossomos/genética , Exossomos/patologia , Biomarcadores Tumorais , Separação Imunomagnética , Gliceraldeído-3-Fosfato Desidrogenases/genética
10.
BMC Nephrol ; 24(1): 24, 2023 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717805

RESUMO

BACKGROUND: Macrophages contribute to epithelial-mesenchymal transition (EMT) in diabetic nephropathy (DN). Exosomal long non-coding RNAs (lncRNAs) derived from macrophages play a major role in transmitting biological information, whereas related studies on DN are rare. Here we investigated the effects of exosomal lncRNAs from high glucose-treated macrophages on EMT. METHODS: High glucose-treated macrophage exosomes (HG-exos) were extracted by coprecipitation and stabilized. Then, mouse renal tubular epithelial cells were treated with HG-exos for 24 h. Expression of E-cadherin, α-smooth muscle actin (α-SMA), and fibronectin was detected by western blotting, qPCR, and immunofluorescence. High-throughput sequencing was then applied to analyze the bioinformatics of HG-exos. RESULTS: HG-exos inhibited the proliferation of tubular epithelial cells. Additionally, HG-exos markedly upregulated α-SMA and fibronectin expression and downregulated E-cadherin expression in tubular epithelial cells, indicating EMT induction. A total of 378 differentially expressed lncRNAs and 674 differentially expressed mRNAs were identified by high-throughput sequencing of HG-exos. Bioinformatics analysis and subsequent qPCR validation suggested 27 lncRNAs were enriched in the EMT-related MAPK pathway. Among them, ENSMUST00000181751.1, XR_001778608.1, and XR_880236.2 showed high homology with humans. CONCLUSION: Exosomes from macrophages induce EMT in DN and lncRNAs in exosomes enriched in the MAPK signaling pathway may be the possible mechanism.


Assuntos
Nefropatias Diabéticas , Exossomos , RNA Longo não Codificante , Humanos , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fibronectinas/metabolismo , Transição Epitelial-Mesenquimal/genética , Exossomos/metabolismo , Células Epiteliais , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Caderinas/genética , Caderinas/metabolismo , Glucose/toxicidade , Glucose/metabolismo , Macrófagos/metabolismo
11.
Regen Med ; 18(2): 181-194, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36597716

RESUMO

Regenerative aesthetics is a burgeoning field for skin rejuvenation and skin health restoration. Exosomes, or extracellular vesicles, represent a new and minimally invasive addition to the regenerative aesthetic toolbox. These nano-sized vesicles contain bioactive cargo with crucial roles in intercellular communication. Exosome technology, while still in its infancy, is now leveraged in regenerative aesthetic medicine due to its multifaceted role in targeting root causes of skin aging and improving overall tissue homeostasis. The main considerations for practice utilization include variation in exosome purification, isolation, storage, scalability and reproducibility. This review aims at highlighting the current and emerging landscape of exosomes in aesthetic medicine including skin rejuvenation and hair restoration.


What is this article about? The purpose of this paper is to review available studies that look at the effects of exosomes in aesthetic medicine and cosmetic surgery. A thorough literature search of all available studies was performed. What were the results? Topical exosomes, although variable in source and method of isolation, are generally considered safe in humans on intact skin. The current published research literature does not yet provide a clear consensus on long-term use for skin rejuvenation or hair restoration, nor does it delineate which patients would benefit most from this technology. There are no currently US FDA-approved exosome products on the market for medical indications. What do the results of this literature review mean? More clinical studies with proper regulatory oversight are needed.


Assuntos
Exossomos , Reprodutibilidade dos Testes , Medicina Regenerativa , Pele , Estética
12.
Technol Cancer Res Treat ; 22: 15330338221149266, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36604966

RESUMO

Cell-to-cell interactions in the intricate microenvironment of tissue have a significant impact on the progression of cancer at every stage. Both cancer cells and stromal cells are responsible for the secretion of soluble chemical compounds as well as membrane-encased components, which both influence and govern the cell-to-cell interactions within the micro-environment of tumor cells. These membrane structures are identified as extracellular vesicles (EVs), which include exosomes and microvesicles. These nanosized vesicles are made up of bilayered proteolipids and have dimensions ranging from 50 to 1000 nm. It has been speculated that extracellular vesicles that originate from cancer cells perform a variety of functions in the development and progression of cancer which may involve the transport of regulatory materials, such as oncogenic proteins between nearby cells and to distant biological locations. In addition, their level in the serum of cancer patients is noticeably higher than those of healthy controls. The release of extracellular vesicles into the extracellular space is a continual process in both healthy and diseased cells. These extracellular vesicles hold molecular signatures that are defining features of health as well as disease. And hence, the EVs present in biological fluids provide unparalleled and noninvasive access to the necessary molecular details about the health status of the cells. Recent discoveries about these complex extracellular organelles have accelerated the discovery of cancer-specific biological markers as well as the development of unique diagnostic tools based on extracellular vesicles. In this mini-review, we aim to highlight the hopes and hypes associated with the applications of extracellular vesicles as biomarkers for cancer diagnosis.


Assuntos
Micropartículas Derivadas de Células , Exossomos , Vesículas Extracelulares , Neoplasias , Humanos , Vesículas Extracelulares/metabolismo , Neoplasias/patologia , Biomarcadores , Exossomos/metabolismo , Micropartículas Derivadas de Células/metabolismo , Microambiente Tumoral
13.
Nucleic Acids Res ; 51(1): 396-419, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36610751

RESUMO

Trypanosoma brucei belongs to a group of protozoans presenting fragmented large subunit rRNA. Its LSU rRNA equivalent to the 25S/28S rRNA of other eukaryotes is split into six fragments, requiring additional processing for removal of the extra spacer sequences. We have used a genetic complementation strategy to further investigate the T. brucei RRP44 nuclease in pre-rRNA maturation. TbRRP44 contains both a PIN and a RNB domain whose homologues are found in association with the exosome complex. We found that the exonucleolytic activity of the RNB domain as well as the physical presence of the PIN domain are essential for TbRRP44 function, while a catalytic site mutation in the PIN domain has no detectable effect on cell growth. A new endonucleolytic cleavage site in ITS1 was identified. In addition to the 5.8S rRNA 3'-end maturation, TbRRP44 is required for degradation of the excised 5'-ETS and for removal of part of ITS1 during maturation of the 18S rRNA 3'-end. TbRRP44 deficiency leads to accumulation of many LSU intermediate precursors, most of them not detected in control cells. TbRRP44 is also required for U3 snoRNA and spliced leader processing, indicating that TbRRP44 may have a wide role in RNA processing in T. brucei.


Assuntos
Exonucleases , Trypanosoma brucei brucei , Exossomos/metabolismo , Expressão Gênica , Precursores de RNA/genética , Precursores de RNA/metabolismo , Processamento Pós-Transcricional do RNA , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , RNA Ribossômico 18S/genética , RNA Ribossômico 18S/metabolismo , Trypanosoma brucei brucei/enzimologia , Exonucleases/metabolismo
14.
J Zhejiang Univ Sci B ; 24(1): 1-14, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36632747

RESUMO

Skeletal muscle plays a paramount role in physical activity, metabolism, and energy balance, while its homeostasis is being challenged by multiple unfavorable factors such as injury, aging, or obesity. Exosomes, a subset of extracellular vesicles, are now recognized as essential mediators of intercellular communication, holding great clinical potential in the treatment of skeletal muscle diseases. Herein, we outline the recent research progress in exosomal isolation, characterization, and mechanism of action, and emphatically discuss current advances in exosomes derived from multiple organs and tissues, and engineered exosomes regarding the regulation of physiological and pathological development of skeletal muscle. These remarkable advances expand our understanding of myogenesis and muscle diseases. Meanwhile, the engineered exosome, as an endogenous nanocarrier combined with advanced design methodologies of biomolecules, will help to open up innovative therapeutic perspectives for the treatment of muscle diseases.


Assuntos
Exossomos , Exossomos/fisiologia , Músculo Esquelético/metabolismo , Comunicação Celular , Homeostase
15.
J Nanobiotechnology ; 21(1): 29, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698192

RESUMO

Liver fibrosis is a chronic liver disease with the presence of progressive wound healing response caused by liver injury. Currently, there are no approved therapies for liver fibrosis. Exosomes derived from human adipose mesenchymal stem cells (hADMSCs-Exo) have displayed a prominent therapeutic effect on liver diseases. However, few studies have evaluated therapeutic effect of hADMSCs-Exo in liver fibrosis and cirrhosis, and its precise mechanisms of action remain unclear. Herein, we investigated anti-fibrotic efficacy of hADMSCs-Exo in vitro and in vivo, and identified important metabolic changes and the detailed mechanism through transcriptomic and metabolomic profiling. We found hADMSCs-Exo could inhibit the proliferation of activated hepatic stellate cells through aggravating apoptosis and arresting G1 phase, effectively inhibiting the expression of profibrogenic proteins and epithelial-to-mesenchymal transition (EMT) in vitro. Moreover, it could significantly block collagen deposition and EMT process, improve liver function and reduce liver inflammation in liver cirrhosis mice model. The omics analysis revealed that the key mechanism of hADMSCs-Exo anti-hepatic fibrosis was the inhibition of PI3K/AKT/mTOR signaling pathway and affecting the changes of metabolites in lipid metabolism, and mainly regulating choline metabolism. CHPT1 activated by hADMSCs-Exo facilitated formation and maintenance of vesicular membranes. Thus, our study indicates that hADMSCs-Exo can attenuate hepatic stellate cell activation and suppress the progression of liver fibrosis, which holds the significant potential of hADMSCs-Exo for use as extracellular nanovesicles-based therapeutics in the treatment of liver fibrosis and possibly other intractable chronic liver diseases.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Animais , Camundongos , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Exossomos/metabolismo , Cirrose Hepática/terapia , Cirrose Hepática/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Colina/metabolismo
16.
Mol Med ; 29(1): 1, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604626

RESUMO

BACKGROUND: Long intergenic non-coding RNA 00963 (LINC00963) is an oncogenic lncRNA in human cancers. However, little is known on how it impacts the pathogenesis of lung adenocarcinoma (LUAD). METHODS: Biological effects on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were examined by CCK-8, colony formation, EdU incorporation, transwell, and immunofluorescence assays, respectively. Macrophage polarization was evaluated by flow cytometry. Ubiquitination of Zeb1 was examined by co-immunoprecipitation. The location of LINC00963 in LUAD tissues and cell lines was tested by FISH assay. The LINC00963/HNRNPA2B1/Siah1 mRNA complex interaction was verified using RNA pull-down and immunoprecipitation assays. The exact roles of LINC00963 were further validated in metastasis and xenograft models. RESULTS: Higher LINC00963 expression in LUAD patients positively correlated with shorter overall survival, higher stages, and metastasis. LINC00963 mainly localized in the cytoplasm and aggravated malignant phenotypes of LUAD cells in vitro and metastasis in vivo. Mechanistically, LINC00963 directly interacted HNRNPA2B1 protein to trigger the degradation of Siah1 mRNA, which inhibited the ubiquitination and degradation of Zeb1. Moreover, exosomal LINC00963 derived from LUAD cells induced M2 macrophage polarization and promoted LUAD growth and metastasis. CONCLUSION: By stabilizing Zeb1 in cancer cells and delivering exosomes to induce M2 macrophage polarization, LINC00963 promoted the malignancy and metastasis of LUAD. Targeting LINC00963 may become a valuable therapeutic target for LUAD.


Assuntos
Adenocarcinoma , Exossomos , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , MicroRNAs/genética , Neoplasias Pulmonares/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Exossomos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Pulmão/patologia , Adenocarcinoma/genética , RNA Mensageiro , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
17.
Nanoscale ; 15(4): 1890-1899, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36606731

RESUMO

Dry eye disease (DED), a complex ocular surface disease with a high prevalence rate, is associated with corneal injury, excess oxidative stress and inflammation. Current therapeutic strategies, including artificial tears and anti-inflammatory agents, are unable to address all the deleterious factors or to achieve a clinical cure due to their temporary or side effects. Here, we prepared a multiple-functional eyedrop based on the deposition of gold nanoparticles (AuNPs) reduced by ascorbic acid (AA) onto the exosomal phospholipid membrane of mesenchymal stem cell (mExo)-derived exosomes in situ (mExo@AA). The therapeutic value of mExo@AA for DED was demonstrated in a mouse DED model. Combining the benefits of mExo and AA, mExo@AA effectively improves corneal epithelium recovery and anti-inflammation capacity, decreases corneal reactive oxygen species, and restores tear secretion without adverse effects. Thus, this study suggests that mExo@AA is effective and safe as a therapeutic agent for the treatment of DED.


Assuntos
Síndromes do Olho Seco , Exossomos , Nanopartículas Metálicas , Camundongos , Animais , Ouro/farmacologia , Soluções Oftálmicas , Ácido Ascórbico/farmacologia , Exossomos/metabolismo , Nanopartículas Metálicas/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Anti-Inflamatórios
18.
Int J Oral Sci ; 15(1): 2, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36596771

RESUMO

Saliva testing is a vital method for clinical applications, for its noninvasive features, richness in substances, and the huge amount. Due to its direct anatomical connection with oral, digestive, and endocrine systems, clinical usage of saliva testing for these diseases is promising. Furthermore, for other diseases that seeming to have no correlations with saliva, such as neurodegenerative diseases and psychological diseases, researchers also reckon saliva informative. Tremendous papers are being produced in this field. Updated summaries of recent literature give newcomers a shortcut to have a grasp of this topic. Here, we focused on recent research about saliva biomarkers that are derived from humans, not from other organisms. The review mostly addresses the proceedings from 2016 to 2022, to shed light on the promising usage of saliva testing in clinical diagnostics. We recap the recent advances following the category of different types of biomarkers, such as intracellular DNA, RNA, proteins and intercellular exosomes, cell-free DNA, to give a comprehensive impression of saliva biomarker testing.


Assuntos
Exossomos , Saliva , Humanos , Saliva/metabolismo , Biomarcadores/metabolismo , RNA , Exossomos/metabolismo
19.
J Nanobiotechnology ; 21(1): 6, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36600299

RESUMO

While several artificial nanodrugs have been approved for clinical treatment of breast tumor, their long-term applications are restricted by unsatisfactory therapeutic outcomes, side reactions and high costs. Conversely, edible plant-derived natural nanotherapeutics (NTs) are source-widespread and cost-effective, which have been shown remarkably effective in disease treatment. Herein, we extracted and purified exosome-like NTs from tea leaves (TLNTs), which had an average diameter of 166.9 nm and a negative-charged surface of - 28.8 mV. These TLNTs contained an adequate slew of functional components such as lipids, proteins and pharmacologically active molecules. In vitro studies indicated that TLNTs were effectively internalized by breast tumor cells (4T1 cells) and caused a 2.5-fold increase in the amount of intracellular reactive oxygen species (ROS) after incubation for 8 h. The high levels of ROS triggered mitochondrial damages and arrested cell cycles, resulting in the apoptosis of tumor cells. The mouse experiments revealed that TLNTs achieved good therapeutic effects against breast tumors regardless of intravenous injection and oral administration through direct pro-apoptosis and microbiota modulation. Strikingly, the intravenous injection of TLNTs, not oral administration, yielded obvious hepatorenal toxicity and immune activation. These findings collectively demonstrate that TLNTs can be developed as a promising oral therapeutic platform for the treatment of breast cancer.


Assuntos
Exossomos , Neoplasias Mamárias Animais , Microbiota , Animais , Camundongos , Exossomos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Mamárias Animais/patologia , Apoptose , Folhas de Planta/metabolismo , Chá , Linhagem Celular Tumoral
20.
Int J Mol Sci ; 24(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614310

RESUMO

Exosomes may function as multifactorial mediators of cell-to-cell communication, playing crucial roles in both physiological and pathological processes. Exosomes released from virus-infected cells may contain RNA and proteins facilitating infection spread. The purpose of our study was to analyze how the small RNA content of exosomes is affected by infection with the influenza A virus (IAV). Exosomes were isolated by ultracentrifugation after hemadsorption of virions and their small RNA content was identified using high-throughput sequencing. As compared to mock-infected controls, 856 RNA transcripts were significantly differentially expressed in exosomes from IAV-infected cells, including fragments of 458 protein-coding (pcRNA), 336 small, 28 long intergenic non-coding RNA transcripts, and 33 pseudogene transcripts. Upregulated pcRNA species corresponded mainly to proteins associated with translation and antiviral response, and the most upregulated among them were RSAD2, CCDC141 and IFIT2. Downregulated pcRNA species corresponded to proteins associated with the cell cycle and DNA packaging. Analysis of differentially expressed pseudogenes showed that in most cases, an increase in the transcription level of pseudogenes was correlated with an increase in their parental genes. Although the role of exosome RNA in IAV infection remains undefined, the biological processes identified based on the corresponding proteins may indicate the roles of some of its parts in IAV replication.


Assuntos
Exossomos , Vírus da Influenza A , Influenza Humana , Humanos , RNA/metabolismo , Vírus da Influenza A/genética , Exossomos/genética , Células Epiteliais/metabolismo , Proteínas/metabolismo , Replicação Viral
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