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Neural Regeneration Research Nov 2022Blood exosomes, which are extracellular vesicles secreted by living cells into the circulating blood, are regarded as a relatively noninvasive novel tool for monitoring... (Review)
Review
Blood exosomes, which are extracellular vesicles secreted by living cells into the circulating blood, are regarded as a relatively noninvasive novel tool for monitoring brain physiology and disease states. An increasing number of blood cargo-loaded exosomes are emerging as potential biomarkers for preclinical and clinical Alzheimer's disease. Therefore, we conducted a meta-analysis and systematic review of molecular biomarkers derived from blood exosomes to comprehensively analyze their diagnostic performance in preclinical Alzheimer's disease, mild cognitive impairment, and Alzheimer's disease. We performed a literature search in PubMed, Web of Science, Embase, and Cochrane Library from their inception to August 15, 2020. The research subjects mainly included Alzheimer's disease, mild cognitive impairment, and preclinical Alzheimer's disease. We identified 34 observational studies, of which 15 were included in the quantitative analysis (Newcastle-Ottawa Scale score 5.87 points) and 19 were used in the qualitative analysis. The meta-analysis results showed that core biomarkers including Aβ, P-T181-tau, P-S396-tau, and T-tau were increased in blood neuron-derived exosomes of preclinical Alzheimer's disease, mild cognitive impairment, and Alzheimer's disease patients. Molecules related to additional risk factors that are involved in neuroinflammation (C1q), metabolism disorder (P-S312-IRS-1), neurotrophic deficiency (HGF), vascular injury (VEGF-D), and autophagy-lysosomal system dysfunction (cathepsin D) were also increased. At the gene level, the differential expression of transcription-related factors (REST) and microRNAs (miR-132) also affects RNA splicing, transport, and translation. These pathological changes contribute to neural loss and synaptic dysfunction. The data confirm that the above-mentioned core molecules and additional risk-related factors in blood exosomes can serve as candidate biomarkers for preclinical and clinical Alzheimer's disease. These findings support further development of exosome biomarkers for a clinical blood test for Alzheimer's disease. This meta-analysis was registered at the International Prospective Register of Systematic Reviews (Registration No. CRD4200173498, 28/04/2020).
PubMed: 35535875
DOI: 10.4103/1673-5374.335832 -
Theranostics 2022Small extracellular vesicles (sEVs) have been proposed as a possible solution to the current lack of therapeutic interventions for endogenous skin regeneration. We... (Meta-Analysis)
Meta-Analysis Review
Small extracellular vesicles (sEVs) have been proposed as a possible solution to the current lack of therapeutic interventions for endogenous skin regeneration. We conducted a systematic review of the available evidence to assess sEV therapeutic efficacy and safety in wound healing and skin regeneration in animal models. 68 studies were identified in Web of Science, Scopus, and PubMed that satisfied a set of prespecified inclusion criteria. We critically analyzed the quality of studies that satisfied our inclusion criteria, with an emphasis on methodology, reporting, and adherence to relevant guidelines (including MISEV2018 and ISCT criteria). Overall, our systematic review and meta-analysis indicated that sEV interventions promoted skin regeneration in diabetic and non-diabetic animal models and influenced various facets of the healing process regardless of cell source, production protocol and disease model. The EV source, isolation methods, dosing regimen, and wound size varied among the studies. Modification of sEVs was achieved mainly by manipulating source cells via preconditioning, nanoparticle loading, genetic manipulation, and biomaterial incorporation to enhance sEV therapeutic potential. Evaluation of potential adverse effects received only minimal attention, although none of the studies reported harmful events. Risk of bias as assessed by the SYRCLE's ROB tool was uncertain for most studies due to insufficient reporting, and adherence to guidelines was limited. In summary, sEV therapy has enormous potential for wound healing and skin regeneration. However, reproducibility and comprehensive evaluation of evidence are challenged by a general lack of transparency in reporting and adherence to guidelines. Methodological rigor, standardization, and risk analysis at all stages of research are needed to promote translation to clinical practice.
Topics: Animals; Biocompatible Materials; Extracellular Vesicles; Reproducibility of Results; Skin; Wound Healing
PubMed: 36185607
DOI: 10.7150/thno.73436 -
Biochimica Et Biophysica Acta.... Jan 2023DNA methylation profiles are in dynamic equilibrium via the initiation of methylation, maintenance of methylation and demethylation, which control gene expression and... (Review)
Review
DNA methylation profiles are in dynamic equilibrium via the initiation of methylation, maintenance of methylation and demethylation, which control gene expression and chromosome stability. Changes in DNA methylation patterns play important roles in carcinogenesis and primarily manifests as hypomethylation of the entire genome and the hypermethylation of individual loci. These changes may be reflected in blood-based DNA, which provides a non-invasive means for cancer monitoring. Previous blood-based DNA detection objects primarily included circulating tumor DNA/cell-free DNA (ctDNA/cfDNA), circulating tumor cells (CTCs) and exosomes. Researchers gradually found that methylation changes in peripheral blood mononuclear cells (PBMCs) also reflected the presence of tumors. Blood-based DNA methylation is widely used in early diagnosis, prognosis prediction, dynamic monitoring after treatment and other fields of clinical research on cancer. The reversible methylation of genes also makes them important therapeutic targets. The present paper summarizes the changes in DNA methylation in cancer based on existing research and focuses on the characteristics of the detection objects of blood-based DNA, including ctDNA/cfDNA, CTCs, exosomes and PBMCs, and their application in clinical research.
Topics: Humans; DNA Methylation; Leukocytes, Mononuclear; Biomarkers, Tumor; Circulating Tumor DNA; Neoplasms; Cell-Free Nucleic Acids
PubMed: 36270476
DOI: 10.1016/j.bbadis.2022.166583 -
Stem Cell Research & Therapy Apr 2023The increasing incidence of osteoporosis in recent years has aroused widespread public concern; however, existing effective treatments are limited. Therefore, new... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The increasing incidence of osteoporosis in recent years has aroused widespread public concern; however, existing effective treatments are limited. Therefore, new osteoporosis treatment methods, including stem cell transplantation and exosome therapy, have been proposed and are gaining momentum. Exosomes are considered to have greater potential for clinical application owing to their immunocompatibility. This study summarises the latest evidence demonstrating the efficacy of exosomes in improving bone loss in the treatment of osteoporosis.
MAIN TEXT
This systematic review and meta-analyses searched PubMed, Embase, and Cochrane Library databases from inception to 26 March 2022 for osteoporosis treatment studies using stem cell-derived exosomes. Six endpoints were selected to determine efficacy: bone mineral density, trabecular bone volume/tissue volume fraction, trabecular number, trabecular separation, trabecular thickness, and cortical thickness. The search generated 366 citations. Eventually, 11 articles that included 15 controlled preclinical trials and 242 experimental animals (rats and mice) were included in the meta-analysis.
CONCLUSION
The results were relatively robust and reliable despite some publication biases, suggesting that exosome treatment increased bone mass, improved bone microarchitecture, and enhanced bone strength compared with placebo treatments. Moreover, stem cell-derived exosomes may favour anabolism over catabolism, shifting the dynamic balance towards bone regeneration.
Topics: Rats; Mice; Animals; Exosomes; Osteoporosis; Bone Density; Bone and Bones; Treatment Outcome
PubMed: 37038180
DOI: 10.1186/s13287-023-03317-4 -
Cancers Sep 2021Cancer is a leading public health issue globally, and diagnosis is often associated with poor outcomes and reduced patient survival. One of the major contributors to the... (Review)
Review
Cancer is a leading public health issue globally, and diagnosis is often associated with poor outcomes and reduced patient survival. One of the major contributors to the fatality resultant of cancer is the development of resistance to chemotherapy, known as chemoresistance. Furthermore, there are limitations in our ability to identify patients that will respond to therapy, versus patients that will develop relapse, and display limited or no response to treatment. This often leads to patients being subjected to multiple futile treatment cycles, and results in a reduction in their quality of life. Therefore, there is an urgent clinical need to develop tools to identify patients at risk of chemoresistance, and recent literature has suggested that small extracellular vesicles, known as exosomes, may be a vital source of information. Extracellular vesicles (EV) are membrane bound vesicles, involved in cell-cell communication, through the transfer of their cargo, which includes proteins, lipids, and miRNAs. A defined exploration strategy was performed in this systematic review in order to provide a compilation of key EV miRNAs which may be predictive of chemoresistance. We searched the PubMed, Science Direct, and Scopus databases using the following keywords: Extracellular vesicles OR exosomes OR EVs AND miRNA AND Chemotherapy OR Chemoresistance OR Cancer Recurrence from 2010 to 2020. We found 31 articles that reported key EV-associated miRNAs involved in cancer recurrence related to chemoresistance. Interestingly, multiple studies of the same tumor type identified different microRNAs, and few studies identified the same ones. Specifically, miR-21, miR-222, and miR-155 displayed roles in response to chemotherapy, and were found to be common in colorectal cancer, ovarian cancer, breast cancer, and diffuse large B cell lymphoma patients (DLBCL). miR-21 and miR-222 were found to favour the development of chemoresistance, whereas miR-155 exhibited a contrasting role, depending on the type of primary tumor. Whilst high levels of miR-155 were found to correlate with chemotherapy resistance in DLBCL, it was found to be predictive of an effective response towards chemotherapy in breast cancer. Thus, further research regarding the roles of these miRNAs would be beneficial in terms of designing novel tools to counteract the progression of cancer in a not-to-distant future.
PubMed: 34572835
DOI: 10.3390/cancers13184608 -
Frontiers in Endocrinology 2022Diabetic nephropathy (DN) is a major microvascular complication of both type 1 and type 2 diabetes mellitus and is the most frequent cause of end-stage renal disease... (Meta-Analysis)
Meta-Analysis
Diabetic nephropathy (DN) is a major microvascular complication of both type 1 and type 2 diabetes mellitus and is the most frequent cause of end-stage renal disease with an increasing prevalence. Presently there is no non-invasive method for differential diagnosis, and an efficient target therapy is lacking. Extracellular vesicles (EV), including exosomes, microvesicles, and apoptotic bodies, are present in various body fluids such as blood, cerebrospinal fluid, and urine. Proteins in EV are speculated to be involved in various processes of disease and reflect the original cells' physiological states and pathological conditions. This systematic review is based on urinary extracellular vesicles studies, which enrolled patients with DN and investigated the proteins in urinary EV. We systematically reviewed articles from the PubMed, Embase, Web of Science databases, and China National Knowledge Infrastructure (CNKI) database until January 4, 2022. The article quality was appraised according to the Newcastle-Ottawa Quality Assessment Scale (NOS). The methodology of samples, isolation and purification techniques of urinary EV, and characterization methods are summarized. Molecular functions, biological processes, and pathways were enriched in all retrievable urinary EV proteins. Protein-protein interaction analysis (PPI) revealed pathways of potential biomarkers. A total of 539 articles were retrieved, and 13 eligible records were enrolled in this systematic review and meta-analysis. And two studies performed mass spectrometry to obtain the proteome profile. Two of them enrolled only T1DM patients, two studies enrolled both patients with T1DM and T2DM, and other the nine studies focused on T2DM patients. In total 988 participants were enrolled, and DN was diagnosed according to UACR, UAER, or decreased GFR. Totally 579 urinary EV proteins were detected and 28 of them showed a potential value to be biomarkers. The results of bioinformatics analysis revealed that urinary EV may participate in DN through various pathways such as angiogenesis, biogenesis of EV, renin-angiotensin system, fluid shear stress and atherosclerosis, collagen degradation, and immune system. Besides that, it is necessary to report results compliant with the guideline of ISEV, in orderto assure repeatability and help for further studies. This systematic review concordance with previous studies and the results of meta-analysis may help to value the methodology details when urinary EV proteins were reported, and also help to deepen the understanding of urinary EV proteins in DN.
Topics: Biomarkers; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Extracellular Vesicles; Humans; Proteome
PubMed: 36034457
DOI: 10.3389/fendo.2022.866252 -
Journal of Clinical Medicine Nov 2019Secretome and extracellular vesicles (EVs) are considered a promising option to exploit mesenchymal stem cells' (MSCs) properties to address knee osteoarthritis (OA).... (Review)
Review
Secretome and extracellular vesicles (EVs) are considered a promising option to exploit mesenchymal stem cells' (MSCs) properties to address knee osteoarthritis (OA). The aim of this systematic review was to analyze both the in vitro and in vivo literature, in order to understand the potential of secretome and EVs as a minimally invasive injective biological approach. A systematic review of the literature was performed on PubMed, Embase, and Web of Science databases up to 31 August 2019. Twenty studies were analyzed; nine in vitro, nine in vitro and in vivo, and two in vivo. The analysis showed an increasing interest in this emerging field, with overall positive findings. Promising in vitro results were documented in terms of enhanced cell proliferation, reduction of inflammation, and down-regulation of catabolic pathways while promoting anabolic processes. The positive in vitro findings were confirmed in vivo, with studies showing positive effects on cartilage, subchondral bone, and synovial tissues in both OA and osteochondral models. However, several aspects remain to be clarified, such as the different effects induced by EVs and secretome, which is the most suitable cell source and production protocol, and the identification of patients who may benefit more from this new biological approach for knee OA treatment.
PubMed: 31689923
DOI: 10.3390/jcm8111867 -
Respiratory Research Apr 2022Chronic Obstructive Pulmonary Disease (COPD) is a common inflammatory disease of the airways characterized by irreversible airflow limitation, ranking the third highest...
BACKGROUND
Chronic Obstructive Pulmonary Disease (COPD) is a common inflammatory disease of the airways characterized by irreversible airflow limitation, ranking the third highest cause of death worldwide. Extracellular vesicles (EVs) are important intercellular communication mediators released by cells into their extracellular environment with the capacity to transfer biological signals. EVs involved in COPD hold great potential to understand disease pathogenesis and identify important biomarkers. This systematic review aims to examine all available research on EVs in the pathogenesis and diagnosis of COPD to identify existing knowledge and support further research within the field.
METHODS
Publications were searched using PubMed and EMBASE with the search terms (Exosomes or extracellular vesicles or microvesicles or microparticles or ectosomes) AND (chronic obstructive pulmonary disease or COPD or emphysema or bronchitis).
RESULTS
Initial search yielded 512 papers of which 142 were manually selected for review and 43 were eligible for analyses. The studies were divided into groups according to the role of EVs in pathogenesis, EV origin and cargo, their role in COPD exacerbations and their diagnostic utility. EVs were found to be involved in the mechanism of pathogenesis of COPD, derived from various cell types, as well as containing modified levels of miRNAs. EVs also varied according to the pathophysiological status of disease, therefore presenting a possible method for COPD diagnosis and progress monitoring.
CONCLUSION
The current findings show the limited but good quality research looking at the role of EVs in COPD, demonstrating the need for more studies to better define and provide further insight into the functional characteristics of EV in COPD pathogenesis.
Topics: Cell Communication; Cell-Derived Microparticles; Exosomes; Extracellular Vesicles; Humans; Pulmonary Disease, Chronic Obstructive
PubMed: 35382831
DOI: 10.1186/s12931-022-01984-0 -
International Journal of Molecular... Mar 2023Despite laparoscopy being a standardized option to diagnose pelvic endometriotic implants, non-invasive biomarkers are necessary to avoid the discomfort of invasive... (Review)
Review
Despite laparoscopy being a standardized option to diagnose pelvic endometriotic implants, non-invasive biomarkers are necessary to avoid the discomfort of invasive procedures. Recent evidence suggests a potential role of microRNAs (miRNAs) as feasible biomarkers for the early diagnosis of endometriosis. Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched PubMed, EMBASE, Scopus, Cochrane Library, and Science Direct in January 2023. We provided no restriction on the country and year of publication, and considered English published articles. We selected studies including patients with endometriosis and describing miRNA regulation in the context of endometriosis. Overall, 45 studies fulfilled the inclusion criteria, and 2045 patients with endometriosis and 1587 controls were screened. Patients were analyzed concerning miRNAs expression and sources, stage of disease, and symptoms, and compared to controls. Among DEMs, the ones with the widest delta between endometriosis patients and controls-Relative Expression ≥ 4 Log2(ratio)-were miR-145, miR-191, miR-195, miR-21-5p, miR-106b-5p, miR-195-5p, miR-451a, miR-200c, miR-20a-5p, and miR-15a-5p. Although the epigenetic regulation is partially unclear, miRNAs are valid biomarkers to diagnose endometriotic lesions in symptomatic and non-symptomatic women. MiRNAs modulation should be clarified, especially during therapies or relapse, to plan targeted management protocols.
Topics: Humans; Female; Endometriosis; Epigenesis, Genetic; MicroRNAs; Biomarkers; Liquid Biopsy
PubMed: 37047088
DOI: 10.3390/ijms24076116 -
International Journal of Molecular... Dec 2022The pathophysiology of allergic rhinitis (AR), one of the most common diseases in the world, is still not sufficiently understood. Extracellular vesicles (EVs), which... (Review)
Review
The pathophysiology of allergic rhinitis (AR), one of the most common diseases in the world, is still not sufficiently understood. Extracellular vesicles (EVs), which are secreted by host and bacteria cells and take part in near and distant intracellular communication, can provide information about AR. Recently, attention has been drawn to the potential use of EVs as biomarkers, vaccines, or transporters for drug delivery. In this review, we present an up-to-date literature overview on EVs in AR to reveal their potential clinical significance in this condition. A comprehensive and systematic literature search was conducted following PRISMA statement guidelines for original, completed articles, available in English concerning EVs and AR. For this purpose, PubMed/MEDLINE, Scopus, Web of Science, and Cochrane, were searched up until 10 Novenmber 2022. From 275 records, 18 articles were included for analysis. The risk of bias was assessed for all studies as low or moderate risk of overall bias using the Office and Health Assessment and Translation Risk of Bias Rating Tool for Human and Animal Studies. We presented the role of exosomes in the pathophysiology of AR and highlighted the possibility of using exosomes as biomarkers and treatment in this disease.
Topics: Animals; Humans; Rhinitis, Allergic; Extracellular Vesicles; Exosomes; Biomarkers; Biological Transport
PubMed: 36613810
DOI: 10.3390/ijms24010367