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Frontiers in Pharmacology 2023Liver injury is a severe liver lesion caused by various etiologies and is one of the main areas of medical research. C.A. Meyer has traditionally been used as medicine... (Review)
Review
Liver injury is a severe liver lesion caused by various etiologies and is one of the main areas of medical research. C.A. Meyer has traditionally been used as medicine to treat diseases and regulate body functions. Ginsenosides are the main active components of ginseng, and their effects on liver injury have been extensively reported. Preclinical studies meeting the inclusion criteria were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wan Fang Data Knowledge Service Platforms. The Stata 17.0 was used to perform the meta-analysis, meta-regression, and subgroup analysis. This meta-analysis included ginsenosides Rb1, Rg1, Rg3, and compound K (CK), in 43 articles. The overall results showed that multiple ginsenosides significantly reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST), affected oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), and catalase (CAT), and reduced levels of inflammatory factor, such as factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6). Additionally, there was a large amount of heterogeneity in the meta-analysis results. Our predefined subgroup analysis shows that the animal species, the type of liver injury model, the duration of treatment, and the administration route may be the sources of some of the heterogeneity. In a word, ginsenosides have good efficacy against liver injury, and their potential mechanisms of action target antioxidant, anti-inflammatory and apoptotic-related pathways. However, the overall methodological quality of our current included studies was low, and more high-quality studies are needed to confirm their effects and mechanisms further.
PubMed: 37251340
DOI: 10.3389/fphar.2023.1184774 -
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 -
The Journal of Investigative Dermatology Mar 2022Cell-based therapy imparts its therapeutic effects through soluble GFs and vesicular bodies such as exosomes. A systematic review with a meta-analysis of preclinical... (Meta-Analysis)
Meta-Analysis
Cell-based therapy imparts its therapeutic effects through soluble GFs and vesicular bodies such as exosomes. A systematic review with a meta-analysis of preclinical studies was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the modified Stroke Therapy Academic Industry Roundtable guidelines to identify exosomes as an archetype biological therapy for dermal wound healing and to provide guidelines for the concentrations to be used in preclinical studies. A total of 51 rodent studies were included in the systematic review and 9 were included in the meta-analysis section. Three independent reviewers cross-screened eligibility and selected studies for quality assessment from 3,064 published studies on exosomes and wound healing. The mean quality scores for all studies were 5.08 ± 0.752 and 5.11 ± 1.13 for systematic review and meta-analysis, respectively. Exosome effects were reported to have the highest efficacy at 7 days (OR = 1.82, 95% confidence interval = 0.69‒2.95) than at 14 days (OR = 2.29, 95% confidence interval = 0.01‒4.56) after administration. Exosomes were reported to regulate all phases of skin wound healing, mostly by the actions of circulating microRNA. The outcome of this review may be used to guide preclinical and clinical studies on the role of exosomes in wound healing.
Topics: Exosomes; Wound Healing
PubMed: 34461128
DOI: 10.1016/j.jid.2021.07.167 -
Medicine Feb 2021Exosomes are polyvesicles that are formed by invagination of intracellular lysosomal particles, and are released into the extracellular matrix after the fusion of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Exosomes are polyvesicles that are formed by invagination of intracellular lysosomal particles, and are released into the extracellular matrix after the fusion of polyvesicular outer membrane and cell membrane. In the body, immune response, antigen presentation, cell migration, cell differentiation and tumor invasion are closely related to tumorigenesis and tumor progression. This study aimed to conduct a meta-analysis for evaluating the clinicopathological, diagnostic and prognostic significance of exosomal expression in gastrointestinal tumors.
METHODS
The original English articles were systematically searched in the online databases. The diagnostic accuracy, prognostic utility and clinicopathological correlation of gastrointestinal tumors were investigated. The quality assessment for studies of diagnostic accuracy II and Newcastle-Ottawa scale were used for quality evaluation, and the data was strictly extracted to judge the deviation of the study.
RESULTS
A total of 14 studies with 1837 gastrointestinal tumor patients were included. The change in exosomal expression showed significant correlation with poor clinicopathological parameters (tumor diameter: combined P = .00024394; differentiation: combined P = 2.796e-08; lymphatic metastasis: P = 9.610e-07; distant metastasis: combined P = .00017326; pathological classification: combined P = .00875213; invasion depth: combined P = 3.504e-08) carcinoembryonic antigen (combined P = . 04458857) and tumor location (combined P = .00145983). The difference in the area under the curve between gastrointestinal tumor patients and healthy people showed an area under the curve of 0.89 (95%Cl 0.85-0.91) and heterogeneity of 0.59, 95% CI=[0.55-0.68]. The sensitivity was 0.88 (95%Cl 0.83 mi 0.91), the specificity was 0.72 (95%Cl 0.63 mi 0.80), and the diagnostic odds ratio was 18 (10-33). The results of survival analysis revealed that the abnormally expressed exosomes were significantly correlated with poor overall survival (hazard ratio =2.81, 95% CI: 2.02-3.93, P=0.013∗ 62.7%∗).
CONCLUSION
The abnormally expressed exosomes might act as auxiliary biomarkers in diagnosing gastrointestinal tumors and demonstrated good prognostic significance in predicting the survival of patients with gastrointestinal tumors.
Topics: Biomarkers, Tumor; Exosomes; Gastrointestinal Neoplasms; Humans; Prognosis
PubMed: 33578545
DOI: 10.1097/MD.0000000000024509 -
International Journal of Molecular... Mar 2023Seminal plasma contains numerous extracellular vesicles (sEVs). Since sEVs are apparently involved in male (in)fertility, this systematic review focused on studies... (Review)
Review
Seminal plasma contains numerous extracellular vesicles (sEVs). Since sEVs are apparently involved in male (in)fertility, this systematic review focused on studies specifically investigating such relationship. Embase, PubMed, and Scopus databases were searched up to 31 December 2022, primarily identifying a total of 1440 articles. After processing for screening and eligibility, 305 studies were selected as they focused on sEVs, and 42 of them were considered eligible because they included the word fertility or a related word such as infertility, subfertility, fertilization, and recurrent pregnancy loss in the title, objective(s), and/or keywords. Only nine of them met the inclusion criteria, namely (a) conducting experiments aimed at associating sEVs with fertility concerns and (b) isolating and adequately characterizing sEVs. Six studies were conducted on humans, two on laboratory animals, and one on livestock. The studies highlighted some sEV molecules, specifically proteins and small non-coding RNAs, that showed differences between fertile and subfertile or infertile males. The content of sEVs was also related to sperm fertilizing capacity, embryo development, and implantation. Bioinformatic analysis revealed that several of the highlighted sEV fertility-related proteins would be cross-linked to each other and involved in biological pathways related to (i) EV release and loading and (ii) plasma membrane organization.
Topics: Pregnancy; Animals; Female; Male; Humans; Semen; Fertility; Infertility, Male; Spermatozoa; Extracellular Vesicles
PubMed: 36902244
DOI: 10.3390/ijms24054818 -
Frontiers in Molecular Neuroscience 2022Extracellular vesicles (EVs) are known to have a significant role in the central nervous system (CNS) and neurodegenerative disease.
INTRODUCTION
Extracellular vesicles (EVs) are known to have a significant role in the central nervous system (CNS) and neurodegenerative disease.
METHODS
PubMed, Scopus, ISI Web of Science, EMBASE, and Google Scholar were used to identify published articles about EV modifications (2012 to Feb 2022).
RESULTS
In total, 1,435 published papers were identified among the searched articles, with 1,128 non-duplicate publications being identified. Following the screening of titles and abstracts, 214 publications were excluded; following the full-text screening of 93 published articles, another 33 publications were excluded. The remaining 60 studies were considered. The kappa statistic of 0.868 indicated that the raters were highly reliable. Furthermore, the inter-reliability and intra-reliability coefficients were found to be 0.931 and 0.908, respectively, indicating strong reliability and consistency between the eligible studies identified by the raters. A total of 27 relevant studies demonstrated the role of EVs as therapeutic and diagnostic biomarkers in neurodegenerative diseases. Of note, 19 and 14 studies, respectively, found EVs to be pioneering in diagnostic and therapeutic roles.
DISCUSSION
EVs play an important role in the central nervous system (CNS), aiding in cell-to-cell communication and serving as a diagnostic marker and therapeutic target in a variety of neurodegenerative diseases. EVs are the home of several proteins [including-synuclein (-syn) and tau proteins], lipids, and genetic materials such as DNA and RNA. The presence of novel miRNAs in EVs suggests biomarkers for the diagnosis and screening of neurodegenerative disorders. Furthermore, EVs play an important role in the pathogenesis of such disorders. This systematic review discussed the current state of EVs' role in neurological diseases, as well as some preclinical studies on the therapeutic and diagnostic potential of EVs.
PubMed: 36504676
DOI: 10.3389/fnmol.2022.1061076 -
International Wound Journal Aug 2023Excellent capability of exosome derived from human adipose-derived stem cell (ADSC) manifested in improving the quality of wound healing with SMD (STD Mean Difference).... (Meta-Analysis)
Meta-Analysis Review
Excellent capability of exosome derived from human adipose-derived stem cell (ADSC) manifested in improving the quality of wound healing with SMD (STD Mean Difference). However, it is still in the preclinical stage and its efficacy remains uncertain. Emphasised the need for a systematic review of preclinical studies to the validity of it in ameliorate wound healing quality which accelerate the clinical application translation. We performed a systematic literature review to identify all published controlled and intervention studies comparing exosome derived from human ADSC with placebo in animal models of wound closure during wound healing. PubMed, Embase and Cochrane were employed. Risk of bias assessed by the SYRCLE tool aimed at preclinical animal studies. Administration of exosome derived from human ADSC extremely improved wound closure compared with controls, which is primary outcome (SMD 1.423, 95% confidence interval (CI) 1.137-1.709 P < .001), the same effect as ADSC. The therapeutic effect is further enhanced by modified ADSC-EV. Other outcomes: density and the number of blood vessels: (SMD 1.593 95% CI 1.007-2.179 P < .001);Fibrosis-related protein expression was highly expressed in the early term of wound healing, decreased in shaping period, which automatically regulates wound collagen deposition. Scar size, number of fibroblast and epithelial cell migration and proliferation expressed were ranked as follows: modified adipose stem cell exosomes > adipose stem cell exosomes > controls. Exosome derived from human ADSC, especially after enrichment for specific non-coding RNA, is a promising approach to improve healing efficiency.
Topics: Animals; Humans; Adipose Tissue; Exosomes; Wound Healing; Diabetes Mellitus, Experimental; Stem Cells
PubMed: 37102269
DOI: 10.1111/iwj.14081 -
Reproductive Biology and Endocrinology... Dec 2022Endometriosis is a chronic, inflammatory gynaecological disease that can have severe negative impacts on quality of life and fertility, placing burden on patients and... (Review)
Review
Endometriosis is a chronic, inflammatory gynaecological disease that can have severe negative impacts on quality of life and fertility, placing burden on patients and the healthcare system. Due to the heterogeneous nature of endometriosis, and the lack of correlation between symptom and surgical disease severity, diagnosis and treatment remain a significant clinical challenge. Extracellular vesicles (EVs) are biologically active particles containing molecular cargo involved in intercellular communication, that can be exploited for diagnostic and therapeutic purposes.We systematically reviewed studies exploring EVs and their role in endometriosis, specifically addressing diagnostic and therapeutic potential and current understanding of pathophysiology. Five databases (Pubmed, Embase, Medline, Web of Science, Google Scholar) were searched for keywords 'endometriosis' and either 'extracellular vesicles' or 'exosomes'.There were 28 studies included in the review. Endometrium derived EVs contribute to the development of endometriosis. EVs derived from endometriosis lesions contribute to angiogenesis, immunomodulation and fibrosis. Such EVs can be detected in blood, with early data demonstrating utility in diagnosis and recurrence detection. EV isolation techniques varied between studies and only eight of twenty-eight studies fully characterised EVs according to current recommended standards. Reporting/type of endometriosis was limited across studies. Varied patient population, type of sample and isolation techniques created bias and difficulty in comparing studies.EVs hold promise for improving care for symptomatic patients who have never had surgery, as well as those with recurrent symptoms after previous surgery. We encourage further EV research in endometriosis with the inclusion of rigorous reporting of both the patient population and technical methodology used, with the ultimate goal of achieving clinical utility for diagnosis, prognosis and eventually treatment.
Topics: Female; Humans; Quality of Life; Extracellular Vesicles; Exosomes; Endometriosis; Cell Communication; Chronic Disease
PubMed: 36544197
DOI: 10.1186/s12958-022-01040-y -
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