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Keywords = EV-hsa-miR-7-5p

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23 pages, 15987 KiB  
Article
Small and Long Non-Coding RNA Analysis for Human Trophoblast-Derived Extracellular Vesicles and Their Effect on the Transcriptome Profile of Human Neural Progenitor Cells
by Jessica A. Kinkade, Pallav Singh, Mohit Verma, Teka Khan, Toshihiko Ezashi, Nathan J. Bivens, R. Michael Roberts, Trupti Joshi and Cheryl S. Rosenfeld
Cells 2024, 13(22), 1867; https://doi.org/10.3390/cells13221867 - 11 Nov 2024
Cited by 3 | Viewed by 1944
Abstract
In mice, the fetal brain is dependent upon the placenta for factors that guide its early development. This linkage between the two organs has given rise to the term, the placenta–brain axis. A similar interrelationship between the two organs may exist in humans. [...] Read more.
In mice, the fetal brain is dependent upon the placenta for factors that guide its early development. This linkage between the two organs has given rise to the term, the placenta–brain axis. A similar interrelationship between the two organs may exist in humans. We hypothesize that extracellular vesicles (EVs) released from placental trophoblast (TB) cells transport small RNA and other informational biomolecules from the placenta to the brain where their contents have pleiotropic effects. Here, EVs were isolated from the medium in which human trophoblasts (TBs) had been differentiated in vitro from induced pluripotent stem cells (iPSC) and from cultured iPSC themselves, and their small RNA content analyzed by bulk RNA-seq. EVs derived from human TB cells possess unique profiles of miRs, including hsa-miR-0149-3p, hsa-302a-5p, and many long non-coding RNAs (lncRNAs) relative to EVs isolated from parental iPSC. These miRs and their mRNA targets are enriched in neural tissue. Human neural progenitor cells (NPCs), generated from the same iPSC, were exposed to EVs from either TB or iPSC controls. Both sets of EVs were readily internalized. EVs from TB cells upregulate several transcripts in NPCs associated with forebrain formation and neurogenesis; those from control iPSC upregulated a transcriptional phenotype that resembled glial cells more closely than neurons. These results shed light on the possible workings of the placenta–brain axis. Understanding how the contents of small RNA within TB-derived EVs affect NPCs might yield new insights, possible biomarkers, and potential treatment strategies for neurobehavioral disorders that originate in utero, such as autism spectrum disorders (ASDs). Full article
(This article belongs to the Special Issue Human Placenta and Trophoblast Cells in Pregnancy Development)
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13 pages, 1378 KiB  
Article
Association Between Dairy Production System and Milk Functionality Based on Analysis of miRNAs in Exosomes from Milk
by Loubna Abou el qassim, Regina Golan-Gerstl, Shimon Reif and Luis J. Royo
Animals 2024, 14(20), 2960; https://doi.org/10.3390/ani14202960 - 14 Oct 2024
Viewed by 1251
Abstract
Dairy farming practices significantly affect the nutritional and functional properties of milk. This study compares miRNAs in milk exosomes from extensive and intensive dairy systems and explores their potential implications for human consumers. Extensive systems are believed to produce milk of higher quality [...] Read more.
Dairy farming practices significantly affect the nutritional and functional properties of milk. This study compares miRNAs in milk exosomes from extensive and intensive dairy systems and explores their potential implications for human consumers. Extensive systems are believed to produce milk of higher quality with better animal welfare compared to intensive systems. Milk samples from eight extensive and nine intensive dairy farms were analysed. Milk-derived extracellular vesicles were isolated through sequential ultracentrifugation and characterised through Dynamic Light Scattering and Nanosight to determine the size and the concentration of the extracellular vesicles, in addition to immunoblotting to ensure the presence of exosome-specific proteins in their membrane. miRNA levels were quantified using RT-qPCR, and metabolic pathways associated with miRNAs showing significant differences between farm groups were analysed. EVs from extensive farms had higher concentrations. Notably, bta-miR-451 levels were significantly higher in milk from extensive farms (p = 0.021). Like human miRNA hsa-miR-451, it is linked to pathways related to Parkinson’s disease and cancer. Our research suggests that milk production in extensive systems not only provides socioeconomic and environmental benefits but may also have positive effects on human health. Further research is warranted to explore the bioactive potential of these miRNAs and their implications for human health. Full article
(This article belongs to the Section Cattle)
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13 pages, 1266 KiB  
Article
MiRNAs in Extracellular Vesicles as Biomarkers in Plasma of Papillary Thyroid Cancer Patients: A Proof-of-Concept Study
by Giuseppa D’Amico, Radha Santonocito, Godfrey Grech, Giuseppa Graceffa, Calogero Cipolla, Federica Scalia, Samuele Raccosta, Mauro Manno, Everly Conway de Macario, Alberto J. L. Macario, Francesco Cappello, Francesca Rappa, Celeste Caruso Bavisotto and Claudia Campanella
Biology 2024, 13(9), 743; https://doi.org/10.3390/biology13090743 - 22 Sep 2024
Cited by 3 | Viewed by 2135
Abstract
Background: The incidence of various types of cancer, for example, papillary thyroid carcinoma (PTC), is on the rise. Since therapeutic success depends greatly on early diagnosis, reliable diagnostic biomarkers must be identified, and easy-to-apply tools for detecting them must urgently be standardized. Here, [...] Read more.
Background: The incidence of various types of cancer, for example, papillary thyroid carcinoma (PTC), is on the rise. Since therapeutic success depends greatly on early diagnosis, reliable diagnostic biomarkers must be identified, and easy-to-apply tools for detecting them must urgently be standardized. Here, we contribute to solving this medical challenge by assessing miRNAs suspected of promoting carcinogenesis in extracellular vesicles (EVs) that can be routinely obtained via liquid biopsy. We profit from current progress in cancerology that provides innovations in liquid biopsy and EVs analysis, along with the identification of miRNAs and chaperone system (CS) components implicated in carcinogenesis. Methods: We measured in EVs obtained from circulating blood plasma from PTC patients the levels of three miRNAs implicated in thyroid cancer, hsa-miR-1-3p, hsa-miR-206, and hsa-miR-221-3p, and most likely involved in the regulation of two members of the CS, Hsp60 and CCT. EVs were isolated from the plasma of patients with PTC and controls with benign goiter (BG) and from the culture medium of a PTC cell line (MDAT32) and were appropriately characterized. Results: The levels of miRNAs determined by RT-qPCR were consistently higher in PTC patients and decreased down to control levels after thyroidectomy. Bioinformatics showed that the miRNAs target genes are associated with the molecular pathogenesis of PTC. Conclusions: Our exploratory study reaffirms the potential in clinics of the selected miRNAs in EVs as useful biomarkers of PTC easily accessible via liquid biopsy, which is minimally invasive and amenable to periodic repetition, an improvement compared to the established fine-needle aspirate biopsy. Full article
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19 pages, 2298 KiB  
Article
Plasma EV-miRNAs as Potential Biomarkers of COVID-19 Vaccine Immune Response in Cancer Patients
by Beatriz Almeida, Tânia R. Dias, Pedro Cruz, Mário Sousa-Pimenta, Ana Luísa Teixeira, Catarina Esteves Pereira, Bruno Costa-Silva, Júlio Oliveira, Rui Medeiros and Francisca Dias
Vaccines 2024, 12(8), 848; https://doi.org/10.3390/vaccines12080848 - 28 Jul 2024
Cited by 2 | Viewed by 2418
Abstract
Cancer patients, prone to severe COVID-19, face immune challenges due to their disease and treatments. Identifying biomarkers, particularly extracellular vesicle (EV)-derived microRNAs (miRNAs), is vital for comprehending their response to COVID-19 vaccination. Therefore, this study aimed to investigate specific EV-miRNAs in the plasma [...] Read more.
Cancer patients, prone to severe COVID-19, face immune challenges due to their disease and treatments. Identifying biomarkers, particularly extracellular vesicle (EV)-derived microRNAs (miRNAs), is vital for comprehending their response to COVID-19 vaccination. Therefore, this study aimed to investigate specific EV-miRNAs in the plasma of cancer patients under active treatment who received the COVID-19 booster vaccine. The selected miRNAs (EV-hsa-miR-7-5p, EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, EV-hsa-miR-145- 5p, and EV-hsa-miR-223-3p) are involved in regulating SARS-CoV-2 spike protein and cytokine release, making them potential biomarkers for vaccination response. The study involved 54 cancer patients. Plasma and serum samples were collected at pre-boost vaccination, and at 3 and 6 months post-boost vaccination. Anti-spike antibody levels were measured. Additionally, RNA was extracted from EVs isolated from plasma and the expression levels of miRNAs were assessed. The results showed a significantly positive antibody response after COVID-19 boost vaccination. The expression levels of EV-hsa-miR-7-5p, EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, and EV-hsa-miR-223-3p increased significantly after 6 months of COVID-19 booster vaccination. Interestingly, an increased expression of certain EV-hsa-miRNAs was positively correlated. Bioinformatic analysis revealed that these correlated miRNAs play a critical role in regulating the targets present in antiviral responses and cytokine production. These findings suggest that EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, and EV-hsa-miR-223-3p may be crucial in immune response induced by mRNA vaccines. Full article
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12 pages, 1639 KiB  
Article
Downregulation of Exosomal hsa-miR-551b-3p in Obesity and Its Link to Type 2 Diabetes Mellitus
by Kseniia V. Dracheva, Irina A. Pobozheva, Kristina A. Anisimova, Stanislav G. Balandov, Maria N. Grunina, Zarina M. Hamid, Dmitriy I. Vasilevsky, Sofya N. Pchelina and Valentina V. Miroshnikova
Non-Coding RNA 2023, 9(6), 67; https://doi.org/10.3390/ncrna9060067 - 2 Nov 2023
Cited by 6 | Viewed by 2410
Abstract
Obesity is a significant risk factor for the development of type 2 diabetes mellitus (T2DM). Adipose tissue dysfunction can affect the pool of circulating exosomal miRNAs, driving concomitant disease in obesity. These exosomal miRNAs can reflect adipose tissue functionality, thus serving as prognostic [...] Read more.
Obesity is a significant risk factor for the development of type 2 diabetes mellitus (T2DM). Adipose tissue dysfunction can affect the pool of circulating exosomal miRNAs, driving concomitant disease in obesity. These exosomal miRNAs can reflect adipose tissue functionality, thus serving as prognostic biomarkers for disease monitoring in case of T2DM. In the present study, we conducted NanoString microRNA profiling of extracellular vesicles (EVs) secreted by adipose tissue of obese patients (body mass index (BMI) > 35) without T2DM and nonobese individuals (BMI < 30) as a control group. Functional and pathway enrichment analysis showed that miRNAs associated with obesity in this study were implicated in insulin signaling and insulin resistance biological pathways. Further, these microRNAs were screened in serum EVs in the following groups: (1) obese patients with T2DM, (2) obese patients without T2DM, and (3) nonobese individuals as a control group. has-miR-551b-3p was shown to be downregulated in adipose tissue EVs, as well as in serum EVs, of patients with obesity without T2DM. At the same time, the serum exosomal hsa-miR-551b-3p content was significantly higher in obese patients with T2DM when compared with obese patients without T2DM and may be a potential biomarker of T2DM development in obesity. Full article
(This article belongs to the Special Issue Non-coding RNA and Diabetes 2.0)
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18 pages, 3415 KiB  
Article
Serum Extracellular Vesicle-Derived hsa-miR-2277-3p and hsa-miR-6813-3p Are Potential Biomarkers for Major Depression: A Preliminary Study
by Issei Seki, Hiroto Izumi, Naomichi Okamoto, Atsuko Ikenouchi, Yasuo Morimoto, Seichi Horie and Reiji Yoshimura
Int. J. Mol. Sci. 2023, 24(18), 13902; https://doi.org/10.3390/ijms241813902 - 9 Sep 2023
Cited by 6 | Viewed by 2028
Abstract
The aim of the present study was to examine the association between miRNA levels in extracellular vesicles (EVs) from serum and the severity of Major Depression (MD). Patient sera from 16 MD cases were collected at our university hospital. The miRNAs contained in [...] Read more.
The aim of the present study was to examine the association between miRNA levels in extracellular vesicles (EVs) from serum and the severity of Major Depression (MD). Patient sera from 16 MD cases were collected at our university hospital. The miRNAs contained in EVs were extracted using a nanofiltration method, and their expression levels were analyzed using miRNA microarrays. Intergroup comparisons were performed to validate the diagnostic performance of miRNAs in EVs. Furthermore, candidate miRNAs in EVs were added to neural progenitor cells, astrocytes, and microglial cells in vitro, and the predicted target genes of the candidate miRNAs were extracted. The predicted target genes underwent enrichment analysis. The expression levels of hsa-miR-6813-3p and hsa-miR-2277-3p were significantly downregulated with increasing depression severity of MD. The pathway enrichment analysis suggests that hsa-miR-6813-3p may be involved in glucocorticoid receptor and gamma-aminobutyric acid receptor signaling. Additionally, hsa-miR-2277-3p was found to be involved in the dopaminergic neural pathway. The analysis of serum miRNAs in EVs suggests that hsa-miR-6813-3p and hsa-miR-2277-3p could serve as novel biomarkers for MD, reflecting its severity. Moreover, these miRNAs in EVs could help understand MD pathophysiology. Full article
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16 pages, 1205 KiB  
Article
IL-6-Mediated Upregulated miRNAs in Extracellular Vesicles Derived from Lund Human Mesencephalic (LUHMES) Cells: Effects on Astrocytes and Microglia
by Kento Nishi, Hiroto Izumi, Taisuke Tomonaga, Chikage Nagano, Yasuo Morimoto and Seichi Horie
Biomolecules 2023, 13(5), 718; https://doi.org/10.3390/biom13050718 - 22 Apr 2023
Cited by 7 | Viewed by 2528
Abstract
Psychological stress plays a major role in depression, and interleukin-6 (IL-6) is elevated during depression and psychological stress. MicroRNAs (miRNAs) in extracellular vesicles (EVs), including exosomes and microvesicles, suppress mRNA expression in other cells when endocytosed. In this study, we analyzed the effect [...] Read more.
Psychological stress plays a major role in depression, and interleukin-6 (IL-6) is elevated during depression and psychological stress. MicroRNAs (miRNAs) in extracellular vesicles (EVs), including exosomes and microvesicles, suppress mRNA expression in other cells when endocytosed. In this study, we analyzed the effect of IL-6 on EVs secreted by neural precursor cells. Cells from the human immortalized neural precursor cell line LUHMES were treated with IL-6. EVs were collected using a nanofiltration method. We then analyzed the uptake of LUHMES-derived EVs by astrocytes (ACs) and microglia (MG). Microarray analysis of miRNAs was performed using EV-incorporated RNA and intracellular RNA from ACs and MG to search for increased numbers of miRNAs. We applied the miRNAs to ACs and MG, and examined the cells for suppressed mRNAs. IL-6 increased several miRNAs in the EVs. Three of these miRNAs were originally low in ACs and MG (hsa-miR-135a-3p, hsa-miR-6790-3p, and hsa-miR-11399). In ACs and MG, hsa-miR-6790-3p and hsa-miR-11399 suppressed four mRNAs involved in nerve regeneration (NREP, KCTD12, LLPH, and CTNND1). IL-6 altered the types of miRNAs in EVs derived from neural precursor cells, by which mRNAs involved in nerve regeneration were decreased in ACs and MG. These findings provide new insights into the involvement of IL-6 in stress and depression. Full article
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15 pages, 2127 KiB  
Article
Identification of Suitable Internal Control miRNAs in Bovine Milk Small Extracellular Vesicles for Normalization in Quantitative Real-Time Polymerase Chain Reaction
by Md. Matiur Rahman, Ryoka Nakanishi, Fumi Tsukada, Shigeo Takashima, Yoshiko Wakihara, Yuji O. Kamatari, Kaori Shimizu, Ayaka Okada and Yasuo Inoshima
Membranes 2023, 13(2), 185; https://doi.org/10.3390/membranes13020185 - 2 Feb 2023
Cited by 3 | Viewed by 2709
Abstract
This study aimed to identify a suitable RNA extraction kit and stable internal control microRNA (miRNA) in bovine milk small extracellular vesicles (sEVs) for a quantitative polymerase chain reaction (qPCR) analysis. Two RNA extraction kits, miRNeasy Micro Kit, and Maxwell RSC miRNA Tissue [...] Read more.
This study aimed to identify a suitable RNA extraction kit and stable internal control microRNA (miRNA) in bovine milk small extracellular vesicles (sEVs) for a quantitative polymerase chain reaction (qPCR) analysis. Two RNA extraction kits, miRNeasy Micro Kit, and Maxwell RSC miRNA Tissue Kit, were compared and evaluated using bovine milk sEVs via qPCR analysis. Five miRNAs, bta-miR-29a, bta-miR-200a, bta-miR-26b, hsa-miR-27b-3p, and hsa-miR-30b-5p, were selected by microarray analyses, and their cycle threshold (Ct) values were further evaluated mathematically using geNorm, NormFinder, BestKeeper, and ∆Ct algorithms. The results revealed that both the miRNeasy Micro Kit and Maxwell RSC miRNA Tissue Kit are useful for the efficient recovery of RNA from bovine milk sEVs. According to the final stability ranking analyzed by RefFinder, hsa-miR-27b-3p and bta-miR-29a can be used as suitable internal control miRNAs in bovine milk sEVs. The study also indicated that using a suitable internal control miRNA may improve the reliability and accuracy of the qPCR analysis for normalization in bovine milk sEVs. To the best of our knowledge, this is the first study to uncover the suitable internal control miRNAs in bovine milk sEVs. Full article
(This article belongs to the Special Issue Lipid Membranes and Their Applications)
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15 pages, 3050 KiB  
Article
The Upregulation of Regenerative Activity for Extracellular Vesicles with Melatonin Modulation in Chemically Defined Media
by Jun Yong Kim, Won-Kyu Rhim, Jiwon Woo, Seung-Gyu Cha, Chun Gwon Park and Dong Keun Han
Int. J. Mol. Sci. 2022, 23(23), 15089; https://doi.org/10.3390/ijms232315089 - 1 Dec 2022
Cited by 12 | Viewed by 2352
Abstract
Extracellular vesicles (EVs) derived from human mesenchymal stem cells (hMSCs) have been widely known to have therapeutic effects by representing characteristics of the origin cells as an alternative for cell-based therapeutics. Major limitations of EVs for clinical applications include low production yields, unknown [...] Read more.
Extracellular vesicles (EVs) derived from human mesenchymal stem cells (hMSCs) have been widely known to have therapeutic effects by representing characteristics of the origin cells as an alternative for cell-based therapeutics. Major limitations of EVs for clinical applications include low production yields, unknown effects from serum impurities, and relatively low bioactivities against dose. In this study, we proposed a cell modulation method with melatonin for human umbilical cord MSCs (hUCMSCs) cultured in serum-free chemically defined media (CDM) to eliminate the effects of serum-derived impurities and promote regeneration-related activities. miRNAs highly associated with regeneration were selected and the expression levels of them were comparatively analyzed among various types of EVs depending on culture conditions. The EVs derived from melatonin-stimulated hUCMSCs in CDM (CDM mEVs) showed the highest expression levels of regeneration-related miRNAs, and 7 times more hsa-let-7b-5p, 5.6 times more hsa-miR-23a-3p, and 5.7 times more hsa-miR-100-5p than others, respectively. In addition, the upregulation of various functionalities, such as wound healing, angiogenesis, anti-inflammation, ROS scavenging, and anti-apoptosis, were proven using in vitro assays by simulating the characteristics of EVs with bioinformatics analysis. The present results suggest that the highly regenerative properties of hUCMSC-derived EVs were accomplished with melatonin stimulation in CDM and provided the potential for clinical uses of EVs. Full article
(This article belongs to the Special Issue Roles and Function of Extracellular Vesicles in Diseases)
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15 pages, 1516 KiB  
Article
Characterization of miRNAs in Milk Small Extracellular Vesicles from Enzootic Bovine Leukosis Cattle
by Fumi Tsukada, Shigeo Takashima, Yoshiko Wakihara, Yuji O. Kamatari, Kaori Shimizu, Ayaka Okada and Yasuo Inoshima
Int. J. Mol. Sci. 2022, 23(18), 10782; https://doi.org/10.3390/ijms231810782 - 15 Sep 2022
Cited by 18 | Viewed by 2642
Abstract
Enzootic bovine leukosis (EBL) is a B-cell lymphosarcoma caused by the bovine leukemia virus (BLV). Most BLV-infected cattle show no clinical signs and only some develop EBL. The pathogenesis of EBL remains unclear and there are no methods for predicting EBL before its [...] Read more.
Enzootic bovine leukosis (EBL) is a B-cell lymphosarcoma caused by the bovine leukemia virus (BLV). Most BLV-infected cattle show no clinical signs and only some develop EBL. The pathogenesis of EBL remains unclear and there are no methods for predicting EBL before its onset. Previously, it was reported that miRNA profiles in milk small extracellular vesicles (sEVs) were affected in cattle in the late stage of BLV infection. It raised a possibility that miRNA profile in milk sEVs from EBL cattle could be also affected. To characterize the difference in milk of EBL cattle and healthy cattle, we examined the miRNA profiles in milk sEVs from four EBL and BLV-uninfected cattle each using microarray analysis. Among the detected miRNAs, three miRNAs—bta-miR-1246, hsa-miR-1290, and hsa-miR-424-5p—which were detectable using quantitative real-time PCR (qPCR) and are associated with cancers in humans—were selected as biomarker candidates for EBL. To evaluate the utility of these miRNAs as biomarkers for EBL, their levels were measured using milk that was freshly collected from 13 EBL and seven BLV-uninfected cattle. bta-miR-1246 and hsa-miR-424-5p, but not hsa-miR-1290, were detected using qPCR and their levels in milk sEVs from EBL cattle were significantly higher than those in BLV-uninfected cattle. bta-miR-1246 and hsa-miR-424-5p in sEVs may promote metastasis by targeting tumor suppressor genes, resulting in increased amounts in milk sEVs in EBL cattle. These results suggest that bta-miR-1246 and hsa-miR-424-5p levels in milk sEVs could serve as biomarkers for EBL. Full article
(This article belongs to the Special Issue Characterization and Biological Function of Milk-Derived miRNAs)
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14 pages, 2498 KiB  
Article
Micro-RNAs from Plasma-Derived Small Extracellular Vesicles as Potential Biomarkers for Tic Disorders Diagnosis
by Yilong Wang, Xuebin Xu, Haihua Chen, Mengying Zhu, Xiaotong Guo and Feng Gao
Brain Sci. 2022, 12(7), 829; https://doi.org/10.3390/brainsci12070829 - 26 Jun 2022
Cited by 6 | Viewed by 2988
Abstract
Tic disorders (TDs) are a series of childhood neuropsychiatric disorders characterized by involuntary motor and/or vocal tics and commonly comorbid with several other psychopathological and/or behavioral disorders (e.g., attention deficit hyperactivity disorder and obsessive–compulsive disorder), which indeed aggravate clinical symptoms and complicate diagnosis [...] Read more.
Tic disorders (TDs) are a series of childhood neuropsychiatric disorders characterized by involuntary motor and/or vocal tics and commonly comorbid with several other psychopathological and/or behavioral disorders (e.g., attention deficit hyperactivity disorder and obsessive–compulsive disorder), which indeed aggravate clinical symptoms and complicate diagnosis and treatment. Micro-RNAs (miRNAs) derived from small extracellular vesicles (sEVs) have been recognized as novel circulating biomarkers of disease. To identify specific miRNAs derived from plasma sEVs for TDs’ diagnosis and prognosis, we used official EV isolation and purification methods to characterize the plasma-derived EV miRNAs from children with different types of TDs. Nanoparticle tracking analysis, transmission electron microscopy, and immunoblot analysis of EV surface markers were applied to confirm the features and quality of sEVs. The RNA sequencing (RNA-seq) approach was adapted to identify novel circulating sEVs-derived miRNAs with altered expression levels in paired comparisons of TDs versus healthy controls (HCs), transient tic disorder (TTD) versus chronic motor or vocal tic disorder (CTD), and TTD versus Tourette Syndrome (TS). GO term and KEGG pathway were performed for functional analysis and the receiver operator curve analysis was followed to test the diagnosis efficacy of differentially expressed miRNAs (DEMs) derived from plasma sEVs among paired groups, namely, TDs versus HCs, TTD versus CTD, and TTD versus TS. As a result, 10 miRNAs (hsa-let-7a, hsa-let-7b, hsa-let-7c, hsa-let-7e, hsa-let-7f, hsa-miR-25-3p, hsa-miR-29a-3p, hsa-miR-30b-5p, hsa-miR-125b-5p, and hsa-miR-1469) have demonstrated a significantly different expression signature in the TDs group compared to HCs with excellent area under curve (AUC) values of 0.99, 0.973, 0.997, 1, 0.99, 0.997, 0.987, 0.993, 0.977, and 0.997, respectively, and the diagnostic efficacy of miRNAs was also estimated for discriminating TTD from CTD or TS. In our research, we finally obtained several potential sEVs-derived miRNA biomarkers to assess the diagnosis and prognosis of TDs. Full article
(This article belongs to the Special Issue New Insights in Neurobiology and Genetics of Tourette Syndrome)
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16 pages, 20926 KiB  
Article
Autocrine Activity of Extracellular Vesicles Induced by Icariin and Its Effectiveness in Glucocorticoid-Induced Injury of Bone Microvascular Endothelial Cells
by Qingyu Zhang, Tengqi Li, Zirong Li, Jike Lu, Xinjie Wu, Fuqiang Gao and Wei Sun
Cells 2022, 11(12), 1921; https://doi.org/10.3390/cells11121921 - 14 Jun 2022
Cited by 17 | Viewed by 3094
Abstract
Glucocorticoids could induce injury and apoptosis of bone microvascular endothelial cells (BMECs) in the femoral head, which is associated with the development of osteonecrosis and osteoporosis. Icariin is a prenylated flavonol glycoside isolated from Epimedium brevicornum, serving as the main active pharmaceutical constituent [...] Read more.
Glucocorticoids could induce injury and apoptosis of bone microvascular endothelial cells (BMECs) in the femoral head, which is associated with the development of osteonecrosis and osteoporosis. Icariin is a prenylated flavonol glycoside isolated from Epimedium brevicornum, serving as the main active pharmaceutical constituent to treat bone loss. Currently, the impact of the autocrine activity of extracellular vesicles (EVs) induced by icariin on the glucocorticoid-induced injury of BMECs is still to be confirmed. In this study, EVs were isolated from BMECs treated with and without icariin by super-speed centrifugation. Although icariin treatment would not significantly change the size and total protein content of BMECs-derived EVs, expression of EVs-carried vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1) was enhanced and numerous miRNAs involved in cell proliferation and apoptosis were upregulated (e.g., hsa-miR-1469 and hsa-miR-133a-5p) or downregulated (e.g., hsa-miR-10b-5p) (p < 0.05). A total of 29 differentially expressed inflammatory factors were detected between the EVs secreted by BMECs from the Icariin-treated group and the Model group. The EVs secreted by BMECs could improve cell viability, decrease cell apoptosis, and promote cell migration and angiogenesis under the intervention of glucocorticoids. Meanwhile, icariin intervention could reinforce these protective effects of BMECs-derived EVs. To sum up, the present study indicates that icariin acts as a promising candidate for treating glucocorticoid-induced injury of BMECs and bone diseases, partially through the autocrine activity of EVs. In vivo or animal studies are still required to better understand the function of BMECs-derived EVs. Full article
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14 pages, 2874 KiB  
Article
Hypoxia-Preconditioned Extracellular Vesicles from Mesenchymal Stem Cells Improve Cartilage Repair in Osteoarthritis
by Bocheng Zhang, Xiaoyuan Tian, Zhenan Qu, Jun Hao and Weiguo Zhang
Membranes 2022, 12(2), 225; https://doi.org/10.3390/membranes12020225 - 16 Feb 2022
Cited by 51 | Viewed by 4894
Abstract
In the past decade, mesenchymal stem cells (MSCs) have been widely used for the treatment of osteoarthritis (OA), and extracellular vesicles (EVs) may play a major role in the efficacy of this treatment. Hypoxia can change the cargo and biological functions of MSC-derived [...] Read more.
In the past decade, mesenchymal stem cells (MSCs) have been widely used for the treatment of osteoarthritis (OA), and extracellular vesicles (EVs) may play a major role in the efficacy of this treatment. Hypoxia can change the cargo and biological functions of MSC-derived EVs (MSC-EVs). The aim of the present study was to determine whether the effects of hypoxia-preconditioned MSC-EVs on OA cartilage repair are superior to normoxia-preconditioned MSC-EVs. By using in vitro and in vivo OA models, we verified that hypoxia-preconditioned MSC-EVs improved chondrocyte proliferation and migration and suppressed chondrocyte apoptosis to a greater extent than normoxia-preconditioned MSC-EVs. Furthermore, we found that hypoxia altered the microRNA expression in MSC-EVs and identified four differentially expressed microRNAs: hsa-miR-181c-5p, hsa-miR-18a-3p, hsa-miR-376a-5p, and hsa-miR-337-5p. Bioinformatics analysis revealed that hypoxic pretreatment may promote cartilage repair by stimulating chondrocyte proliferation and migration and suppressing chondrocyte apoptosis through the miRNA-18-3P/JAK/STAT or miRNA-181c-5p/MAPK signaling pathway. Therefore, hypoxia-preconditioned EVs may be a novel treatment for OA. Full article
(This article belongs to the Special Issue Cell Membrane Vesicles)
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15 pages, 1363 KiB  
Article
Small Non-Coding RNA Profiling in Plasma Extracellular Vesicles of Bladder Cancer Patients by Next-Generation Sequencing: Expression Levels of miR-126-3p and piR-5936 Increase with Higher Histologic Grades
by Alexandru A. Sabo, Giovanni Birolo, Alessio Naccarati, Mihnea P. Dragomir, Serena Aneli, Alessandra Allione, Marco Oderda, Marco Allasia, Paolo Gontero, Carlotta Sacerdote, Paolo Vineis, Giuseppe Matullo and Barbara Pardini
Cancers 2020, 12(6), 1507; https://doi.org/10.3390/cancers12061507 - 9 Jun 2020
Cited by 39 | Viewed by 4431
Abstract
Bladder cancer (BC) is the tenth most frequent cancer worldwide. Due to the need for recurrent cystoscopies and the lack of non-invasive biomarkers, BC is associated with a high management burden. In this respect, small non-coding RNAs (sncRNAs) have been investigated in urine [...] Read more.
Bladder cancer (BC) is the tenth most frequent cancer worldwide. Due to the need for recurrent cystoscopies and the lack of non-invasive biomarkers, BC is associated with a high management burden. In this respect, small non-coding RNAs (sncRNAs) have been investigated in urine as possible biomarkers for BC, but in plasma their potential has not yet been defined. The expression levels of sncRNAs contained in plasma extracellular vesicles (EVs) from 47 men with BC and 46 healthy controls were assessed by next-generation sequencing. The sncRNA profiles were compared with urinary profiles from the same subjects. miR-4508 resulted downregulated in plasma EVs of muscle-invasive BC patients, compared to controls (adj-p = 0.04). In World Health Organization (WHO) grade 3 (G3) BC, miR-126-3p was upregulated both in plasma EVs and urine, when compared to controls (for both, adj-p < 0.05). Interestingly, two sncRNAs were associated with the risk class: miR-4508 with a downward trend going from controls to high risk BC, and piR-hsa-5936 with an upward trend (adj-p = 0.04 and adj-p = 0.05, respectively). Additionally, BC cases with low expression of miR-185-5p and miR-106a-5p or high expression of miR-10b-5p showed shorter survival (adj-p = 0.0013, adj-p = 0.039 and adj-p = 0.047, respectively). SncRNAs from plasma EVs could be diagnostic biomarkers for BC, especially in advanced grade. Full article
(This article belongs to the Special Issue Pathogenesis and Diagnosis of Genitourinary Cancer)
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17 pages, 7873 KiB  
Article
Extracellular Vesicles Enriched in hsa-miR-301a-3p and hsa-miR-1293 Dynamics in Clear Cell Renal Cell Carcinoma Patients: Potential Biomarkers of Metastatic Disease
by Francisca Dias, Ana Luísa Teixeira, Inês Nogueira, Mariana Morais, Joana Maia, Cristian Bodo, Marta Ferreira, Alexandra Silva, Manuela Vilhena, João Lobo, José Pedro Sequeira, Joaquina Maurício, Jorge Oliveira, Klaas Kok, Bruno Costa-Silva and Rui Medeiros
Cancers 2020, 12(6), 1450; https://doi.org/10.3390/cancers12061450 - 2 Jun 2020
Cited by 42 | Viewed by 5342
Abstract
Clear cell renal cell carcinoma (ccRCC) is the most aggressive subtype of kidney cancer and up to 40% of patients submitted to surgery with a curative intent will relapse. Thus, the aim of this study was to analyze the applicability of an Extracellular [...] Read more.
Clear cell renal cell carcinoma (ccRCC) is the most aggressive subtype of kidney cancer and up to 40% of patients submitted to surgery with a curative intent will relapse. Thus, the aim of this study was to analyze the applicability of an Extracellular vesicle (EV) derived miRNA profile as potential prognosis biomarkers in ccRCC patients. We analyzed a nine-miRNA profile in plasma EVs from 32 ccRCC patients with localized disease (before and after surgery) and in 37 patients with metastatic disease. We observed that the levels of EV-derived hsa-miR-25-3p, hsa-miR-126-5p, hsa-miR-200c-3p, and hsa-miR-301a-3p decreased after surgery, whereas hsa-miR-1293 EV-levels increased. Furthermore, metastatic patients presented higher levels of hsa-miR-301a-3p and lower levels of hsa-miR-1293 when compared to patients with localized disease after surgery. Functional enrichment analysis of the targets of the four miRNAs that decreased after surgery resulted in an enrichment of terms related to cell cycle, proliferation, and metabolism, suggesting that EV-miRNA enrichment in the presence of the tumor could represent an epigenetic mechanism to sustain tumor development. Taken together, these results suggest that EVs content varies depending on the presence or absence of the disease and that an increase of EV-derived hsa-miR-301a-3p, and decrease of EV-derived hsa-miR-1293, may be potential biomarkers of metastatic ccRCC. Full article
(This article belongs to the Special Issue Noncoding RNAs in Renal Cell Carcinoma Landscape)
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