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Journal of Extracellular Vesicles Nov 2023Extracellular vesicles (EVs) play a crucial role in pregnancy, revealed by the presence of placental-derived EVs in maternal blood, their in vitro functionality, and... (Review)
Review
Extracellular vesicles (EVs) play a crucial role in pregnancy, revealed by the presence of placental-derived EVs in maternal blood, their in vitro functionality, and their altered cargo in pregnancy pathologies. These EVs are thought to be involved in the development of pregnancy pathologies, such as pre-eclampsia, pre-term birth, and fetal growth restriction, and have been suggested as a source of biomarkers for gestational diseases. However, to accurately interpret their function and biomarker potential, it is necessary to critically evaluate the EV isolation and characterization methodologies used in pregnant cohorts. In this systematic scoping review, we collated the results from 152 studies that have investigated EVs in the blood of pregnant women, and provide a detailed analysis of the EV isolation and characterization methodologies used. Our findings indicate an overall increase in EV concentrations in pregnant compared to non-pregnant individuals, an increased EV count as gestation progresses, and an increased EV count in some pregnancy pathologies. We highlight the need for improved standardization of methodology, greater focus on gestational changes in EV concentrations, and further investigations into the functionality of EVs. Our review suggests that EVs hold great promise as diagnostic and translational tools for gestational diseases. However, to fully realize their potential, it is crucial to improve the standardization and reliability of EV isolation and characterization methodologies, and to gain a better understanding of their functional roles in pregnancy pathologies.
Topics: Pregnancy; Female; Humans; Extracellular Vesicles; Placenta; Reproducibility of Results; Pre-Eclampsia
PubMed: 37974377
DOI: 10.1002/jev2.12377 -
BMC Cancer Oct 2023Extracellular vesicles (EVs) hold promise for improving our understanding of radiotherapy response in glioblastoma due to their role in intercellular communication...
Shooting the messenger: a systematic review investigating extracellular vesicle isolation and characterisation methods and their influence on understanding extracellular vesicles-radiotherapy interactions in glioblastoma.
BACKGROUND
Extracellular vesicles (EVs) hold promise for improving our understanding of radiotherapy response in glioblastoma due to their role in intercellular communication within the tumour microenvironment (TME). However, methodologies to study EVs are evolving with significant variation within the EV research community.
METHODS
We conducted a systematic review to critically appraise EV isolation and characterisation methodologies and how this influences our understanding of the findings from studies investigating radiotherapy and EV interactions in glioblastoma. 246 articles published up to 24/07/2023 from PubMed and Web of Science were identified using search parameters related to radiotherapy, EVs, and glioblastoma. Two reviewers evaluated study eligibility and abstracted data.
RESULTS
In 26 articles eligible for inclusion (16 investigating the effects of radiotherapy on EVs, five investigating the effect of EVs on radiation response, and five clinical studies), significant heterogeneity and frequent omission of key characterisation steps was identified, reducing confidence that the results are related to EVs and their cargo as opposed to co-isolated bioactive molecules. However, the results are able to clearly identify interactions between EVs and radiotherapy bi-directionally within different cell types within the glioblastoma TME. These interactions facilitate transferable radioresistance and oncogenic signalling, highlighting that EVs are an important component in the variability of glioblastoma radiotherapy response.
CONCLUSIONS
Future multi-directional investigations interrogating the whole TME are required to improve subsequent clinical translation, and all studies should incorporate up to date controls and reporting requirements to increase the validity of their findings. This would be facilitated by increased collaboration between less experienced and more experienced EV research groups.
Topics: Humans; Glioblastoma; Signal Transduction; Cell Communication; Extracellular Vesicles; Tumor Microenvironment
PubMed: 37798728
DOI: 10.1186/s12885-023-11437-6 -
International Journal of Molecular... Feb 2024Standard non-melanoma skin cancer (NMSC) treatment involves surgery, recently combined with chemotherapy or immunotherapy in cases of advanced tumors. EVs, including... (Review)
Review
Standard non-melanoma skin cancer (NMSC) treatment involves surgery, recently combined with chemotherapy or immunotherapy in cases of advanced tumors. EVs, including exosomes, are integral to carcinogenesis, and are found in NMSC releasing mediators impacting tumor progression. Nevertheless, the precise intercellular signaling role of NMSC-derived EVs remains unclear. This review aims to elucidate their potential role in NMSC diagnosis and treatment. This systematic review encompassed literature searches in electronic databases from inception to September 2023, based on certain inclusion and exclusion criteria, addressing NMSC-derived EVs, their molecular cargo, and their implications in the diagnosis, prognosis, and treatment of NMSC. Key components were identified. Extracellular vesicle (EV) proteins and RNA have emerged as diagnostic biomarkers in EV-based liquid biopsy. Circular RNA CYP24A1, known for its molecular stability, holds promise as a diagnostic biomarker. Long noncoding RNAs (lincRNA-PICSAR) and Desmoglein 2 (DSg2) are linked to drug resistance, serving as prognostic biomarkers. EV mediators are being actively investigated for their potential role as drug delivery agents. In conclusion, this systematic review showed that NMSC-derived EVs display promise as therapeutic targets and diagnostic biomarkers. Further research is imperative to fully comprehend EV mechanisms and explore their potential in cancer diagnosis and treatment.
Topics: Humans; Extracellular Vesicles; Exosomes; Liquid Biopsy; Skin Neoplasms; Biomarkers
PubMed: 38473864
DOI: 10.3390/ijms25052617 -
CNS Neuroscience & Therapeutics Dec 2023Parkinsonian disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Parkinsonian disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), share early motor symptoms but have distinct pathophysiology. As a result, accurate premortem diagnosis is challenging for neurologists, hindering efforts for disease-modifying therapeutic discovery. Extracellular vesicles (EVs) contain cell-state-specific biomolecules and can cross the blood-brain barrier to the peripheral circulation, providing a unique central nervous system (CNS) insight. This meta-analysis evaluated blood-isolated neuronal and oligodendroglial EVs (nEVs and oEVs) α-synuclein levels in Parkinsonian disorders.
METHODS
Following PRISMA guidelines, the meta-analysis included 13 studies. An inverse-variance random-effects model quantified effect size (SMD), QUADAS-2 assessed risk of bias and publication bias was evaluated. Demographic and clinical variables were collected for meta-regression.
RESULTS
The meta-analysis included 1,565 patients with PD, 206 with MSA, 21 with DLB, 172 with PSP, 152 with CBS and 967 healthy controls (HCs). Findings suggest that combined concentrations of nEVs and oEVs α-syn is higher in patients with PD compared to HCs (SMD = 0.21, p = 0.021), while nEVs α-syn is lower in patients with PSP and CBS compared to patients with PD (SMD = -1.04, p = 0.0017) or HCs (SMD = -0.41, p < 0.001). Additionally, α-syn in nEVs and/or oEVs did not significantly differ in patients with PD vs. MSA, contradicting the literature. Meta-regressions show that demographic and clinical factors were not significant predictors of nEVs or oEVs α-syn concentrations.
CONCLUSION
The results highlight the need for standardized procedures and independent validations in biomarker studies and the development of improved biomarkers for distinguishing Parkinsonian disorders.
Topics: Humans; alpha-Synuclein; Biomarkers; Central Nervous System; Extracellular Vesicles; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders
PubMed: 37416941
DOI: 10.1111/cns.14341 -
Frontiers in Pharmacology 2023Extracellular vesicles (EVs) mediate inflammation, immune responses, gut barrier integrity, and intestinal homeostasis. Recently, the application of EVs in the...
Extracellular vesicles (EVs) mediate inflammation, immune responses, gut barrier integrity, and intestinal homeostasis. Recently, the application of EVs in the treatment of inflammatory bowel disease (IBD) has been under intensive focus. Some studies have been conducted in animal models of colitis, while systematic reviews and meta-analyses are lacking. The current study aimed to conduct a systematic review and meta-analysis of studies investigating the efficacy of EVs on IBD. A systematic retrieval of all studies in PubMed, EMBASE, MEDLINE, Web of Science, and Cochrane Library reported the effects of EVs in the colitis model up to 22 June 2023. The methodological quality was assessed based on SYRCLE's risk of bias (RoB) tool. Disease activity index (DAI), myeloperoxidase activity (MPO), histopathological score (HS), and inflammatory cytokines (TNF-α, NF-κB, IL-1β, IL-6, and IL-10) were extracted as analysis indicators by Web Plot Digitizer 4.5. A meta-analysis was performed to calculate the standardized mean difference and 95% confidence interval using random-effect models by Review Manager 5.3 and STATA 14.0 software. A total of 21 studies were included in this meta-analysis. Although the heterogeneity between studies and the potential publication bias limits confidence in the extent of the benefit, EV treatment was superior to the control in the colitis evaluation with reduced DAI, HS, MPO activity, and pro-inflammatory cytokines, including TNF-α, NF-κB, IL-1β, and IL-6, while increasing the content of anti-inflammatory cytokine IL-10 (all < 0.05). Our meta-analysis results supported the protective effect of EVs on colitis rodent models based on their potential role in IBD therapy and propelling the field toward clinical studies.
PubMed: 37954844
DOI: 10.3389/fphar.2023.1260134 -
Neural Regeneration Research Nov 2023Although there are challenges in treating traumatic central nervous system diseases, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have recently proven...
Although there are challenges in treating traumatic central nervous system diseases, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have recently proven to be a promising non-cellular therapy. We comprehensively evaluated the efficacy of mesenchymal stem cell-derived extracellular vesicles in traumatic central nervous system diseases in this meta-analysis based on preclinical studies. Our meta-analysis was registered at PROSPERO (CRD42022327904, May 24, 2022). To fully retrieve the most relevant articles, the following databases were thoroughly searched: PubMed, Web of Science, The Cochrane Library, and Ovid-Embase (up to April 1, 2022). The included studies were preclinical studies of mesenchymal stem cell-derived extracellular vesicles for traumatic central nervous system diseases. The Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)'s risk of bias tool was used to examine the risk of publication bias in animal studies. After screening 2347 studies, 60 studies were included in this study. A meta-analysis was conducted for spinal cord injury (n = 52) and traumatic brain injury (n = 8). The results indicated that mesenchymal stem cell-derived extracellular vesicles treatment prominently promoted motor function recovery in spinal cord injury animals, including rat Basso, Beattie and Bresnahan locomotor rating scale scores (standardized mean difference [SMD]: 2.36, 95% confidence interval [CI]: 1.96-2.76, P < 0.01, I = 71%) and mouse Basso Mouse Scale scores (SMD = 2.31, 95% CI: 1.57-3.04, P = 0.01, I = 60%) compared with controls. Further, mesenchymal stem cell-derived extracellular vesicles treatment significantly promoted neurological recovery in traumatic brain injury animals, including the modified Neurological Severity Score (SMD = -4.48, 95% CI: -6.12 to -2.84, P < 0.01, I = 79%) and Foot Fault Test (SMD = -3.26, 95% CI: -4.09 to -2.42, P = 0.28, I = 21%) compared with controls. Subgroup analyses showed that characteristics may be related to the therapeutic effect of mesenchymal stem cell-derived extracellular vesicles. For Basso, Beattie and Bresnahan locomotor rating scale scores, the efficacy of allogeneic mesenchymal stem cell-derived extracellular vesicles was higher than that of xenogeneic mesenchymal stem cell-derived extracellular vesicles (allogeneic: SMD = 2.54, 95% CI: 2.05-3.02, P = 0.0116, I = 65.5%; xenogeneic: SMD: 1.78, 95%CI: 1.1-2.45, P = 0.0116, I = 74.6%). Mesenchymal stem cell-derived extracellular vesicles separated by ultrafiltration centrifugation combined with density gradient ultracentrifugation (SMD = 3.58, 95% CI: 2.62-4.53, P < 0.0001, I = 31%) may be more effective than other EV isolation methods. For mouse Basso Mouse Scale scores, placenta-derived mesenchymal stem cell-derived extracellular vesicles worked better than bone mesenchymal stem cell-derived extracellular vesicles (placenta: SMD = 5.25, 95% CI: 2.45-8.06, P = 0.0421, I = 0%; bone marrow: SMD = 1.82, 95% CI: 1.23-2.41, P = 0.0421, I = 0%). For modified Neurological Severity Score, bone marrow-derived MSC-EVs worked better than adipose-derived MSC-EVs (bone marrow: SMD = -4.86, 95% CI: -6.66 to -3.06, P = 0.0306, I = 81%; adipose: SMD = -2.37, 95% CI: -3.73 to -1.01, P = 0.0306, I = 0%). Intravenous administration (SMD = -5.47, 95% CI: -6.98 to -3.97, P = 0.0002, I = 53.3%) and dose of administration equal to 100 μg (SMD = -5.47, 95% CI: -6.98 to -3.97, P < 0.0001, I = 53.3%) showed better results than other administration routes and doses. The heterogeneity of studies was small, and sensitivity analysis also indicated stable results. Last, the methodological quality of all trials was mostly satisfactory. In conclusion, in the treatment of traumatic central nervous system diseases, mesenchymal stem cell-derived extracellular vesicles may play a crucial role in promoting motor function recovery.
PubMed: 37282470
DOI: 10.4103/1673-5374.371376 -
Diagnostic Pathology Mar 2024Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis... (Review)
Review
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis and monitoring disease progression, today's diagnoses are based on ruling out other diseases, neurography, and electromyography examination, which takes a time-consuming procedure.
METHODS
PubMed, ScienceDirect, and Web of Science were explored to extract articles published from January 2015 to June 2023. In the searching strategy following keywords were included; amyotrophic lateral sclerosis, biomarkers, cerebrospinal fluid, serum, and plama.
RESULTS
A total number of 6 studies describing fluid-based exosomal biomarkers were included in this study. Aggregated proteins including SOD1, TDP-43, pTDP-43, and FUS could be detected in the microvesicles (MVs). Moreover, TDP-43 and NFL extracted from plasma exosomes could be used as prognostic biomarkers. Also, downregulated miR-27a-3p detected through exoEasy Maxi and exoQuick Kit in the plasma could be measured as a diagnostic biomarker. Eventually, the upregulated level of CORO1A could be used to monitor disease progression.
CONCLUSION
Based on the results, each biomarker alone is insufficient to evaluate ALS. CNS-derived exosomes contain multiple ALS-related biomarkers (SOD1, TDP-43, pTDP-43, FUS, and miRNAs) that are detectable in cerebrospinal fluid and blood is a proper alternation. Exosome detecting kits listed as exoEasy, ExoQuick, Exo-spin, ME kit, ExoQuick Plus, and Exo-Flow, are helpful to reach this purpose.
Topics: Humans; Exosomes; Amyotrophic Lateral Sclerosis; Superoxide Dismutase-1; Biomarkers; DNA-Binding Proteins; Disease Progression
PubMed: 38429818
DOI: 10.1186/s13000-024-01473-6 -
Cureus Aug 2023Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer with several risk factors. Exosomes are extracellular vesicles generated by the fusion of... (Review)
Review
Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer with several risk factors. Exosomes are extracellular vesicles generated by the fusion of multivesicular structures with the cell membrane and play an important role as intercellular messengers. MicroRNA (miRNA) is a noncoding RNA and regulates post-transcriptional modification. The present systematic review aims to identify and correlate the possible association and role of circulating exosomes with OSCC. Using the search strategy, articles fulfilling the inclusion criteria, published between January 2012 to March 2022, were retrieved from online databases including PubMed, Scopus, Web of Science, and Cochrane Library. About 904 articles were found using an electronic database and a human search. After reviewing the titles and abstracts, 614 studies were eliminated, and duplicate articles were removed. Five studies were included in this systematic review. Circulating exosomal expression of miRNA27, miRNA 21, and miRNA 155 showed significant upregulation in OSCC patients. Circulating exosomes could be potential biomarkers to be used in the detection of patients with OSCC. More studies are warranted in this area to gain a better understanding of the pathophysiology of OSCC and the function of molecular markers from circulating exosomes. Understanding the role of molecular markers from circulating exosomes in pathogenesis will provide a better understanding of the development of the disease, necessitating more study in this area. According to this review, circulating exosomes might be a potential approach to the identification of OSCC.
PubMed: 37692575
DOI: 10.7759/cureus.43235 -
Archives of Oral Biology Sep 2024Exosomes are extracellular vesicles found in saliva and other body fluids. These vesicles range in size from 30 to 150 nm and play a crucial role in intercellular... (Review)
Review
OBJECTIVE
Exosomes are extracellular vesicles found in saliva and other body fluids. These vesicles range in size from 30 to 150 nm and play a crucial role in intercellular communication, transporting different biomolecules, actively targeting cells. These vesicles regulate both physiological and pathological processes within recipient cells. MicroRNAs (miRs) are transported within exosomes and are delivered to target cells where they influence signaling pathways, taking on a crucial regulatory role in oncogenesis; for example, they are implicated in progression and infiltration of various cancers, such as head and neck squamous cell carcinoma (HNSCC).
MATERIAL AND METHODS
A systematic literature search based on specific keywords, according to the PRISMA guidelines, was carried out on PubMed, Web of Science, Scopus, and Google Scholar. Only original articles were selected during this review. The risk of bias was assessed by QUADAS-2.
RESULTS
At the end of the selection process 9 articles were included. In these studies, 41 miRs showed differential expression between healthy subjects and patient with HNSCC. The techniques varied among studies for the extraction and analysis of exosomal miRs. We presented also salivary exosomal miRs pathways, to give insights about pathogenetic mechanisms.
CONCLUSIONS
Exosomal microRNA are promising biomarkers for HNSCC detection. MiR-10b-5p, miR-486-5p, miR-24-3p, miR-412-3p, and miR-512-3p are the most promising markers applicable to diagnostics, while miR-1307-5p and miR-519c-3p resulted overexpressed and correlated to worse survival outcomes.
Topics: Humans; Exosomes; MicroRNAs; Saliva; Biomarkers, Tumor; Prognosis; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 38879952
DOI: 10.1016/j.archoralbio.2024.106012 -
International Journal of Molecular... Jul 2023Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. Tissue reorganization at the site of the epileptogenic focus is accompanied by changes in the... (Review)
Review
Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. Tissue reorganization at the site of the epileptogenic focus is accompanied by changes in the expression patterns of protein molecules. The study of mRNA and its corresponding proteins is crucial for understanding the pathogenesis of the disease. Protein expression profiles do not always directly correlate with the levels of their transcripts; therefore, it is protein profiling that is no less important for understanding the molecular mechanisms and biological processes of TLE. The study and annotation of proteins that are statistically significantly different in patients with TLE is an approach to search for biomarkers of this disease, various stages of its development, as well as a method for searching for specific targets for the development of a further therapeutic strategy. When writing a systematic review, the following aggregators of scientific journals were used: MDPI, PubMed, ScienceDirect, Springer, and Web of Science. Scientific articles were searched using the following keywords: "proteomic", "mass-spectrometry", "protein expression", "temporal lobe epilepsy", and "biomarkers". Publications from 2003 to the present have been analyzed. Studies of brain tissues, experimental models of epilepsy, as well as biological fluids, were analyzed. For each of the groups, aberrantly expressed proteins found in various studies were isolated. Most of the studies omitted important characteristics of the studied patients, such as: duration of illness, type and response to therapy, gender, etc. Proteins that overlap across different tissue types and different studies have been highlighted: DPYSL, SYT1, STMN1, APOE, NME1, and others. The most common biological processes for them were the positive regulation of neurofibrillary tangle assembly, the regulation of amyloid fibril formation, lipoprotein catabolic process, the positive regulation of vesicle fusion, the positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway, removal of superoxide radicals, axon extension, and the regulation of actin filament depolymerization. MS-based proteomic profiling for a relevant study must accept a number of limitations, the most important of which is the need to compare different types of neurological and, in particular, epileptic disorders. Such a criterion could increase the specificity of the search work and, in the future, lead to the discovery of biomarkers for a particular disease.
Topics: Adult; Humans; Epilepsy, Temporal Lobe; Epilepsy; Proteins; Mass Spectrometry; Biomarkers; Temporal Lobe
PubMed: 37446307
DOI: 10.3390/ijms241311130