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Theranostics 2022In recent decades, extracellular vesicles (EVs), as bioactive cell-secreted nanoparticles which are involved in various physiological and pathological processes... (Review)
Review
In recent decades, extracellular vesicles (EVs), as bioactive cell-secreted nanoparticles which are involved in various physiological and pathological processes including cell proliferation, immune regulation, angiogenesis and tissue repair, have emerged as one of the most attractive nanotherapeutics for regenerative medicine. Herein we provide a systematic review of the latest progress of EVs for regenerative applications. Firstly, we will briefly introduce the biogenesis, function and isolation technology of EVs. Then, the underlying therapeutic mechanisms of the native unmodified EVs and engineering strategies of the modified EVs as regenerative entities will be discussed. Subsequently, the main focus will be placed on the tissue repair and regeneration applications of EVs on various organs including brain, heart, bone and cartilage, liver and kidney, as well as skin. More importantly, current clinical trials of EVs for regenerative medicine will also be briefly highlighted. Finally, the future challenges and insightful perspectives of the currently developed EV-based nanotherapeutics in biomedicine will be discussed. In short, the bioactive EV-based nanotherapeutics have opened new horizons for biologists, chemists, nanoscientists, pharmacists, as well as clinicians, making possible powerful tools and therapies for regenerative medicine.
Topics: Extracellular Vesicles; Kidney; Nanoparticles; Regenerative Medicine; Wound Healing
PubMed: 35836815
DOI: 10.7150/thno.72812 -
Journal of the American Academy of... Jun 2020The clinical, histologic, and immunopathologic features of IgA pemphigus have not been studied on a large scale.
BACKGROUND
The clinical, histologic, and immunopathologic features of IgA pemphigus have not been studied on a large scale.
OBJECTIVE
To synthesize existing data on the epidemiologic, clinical, histologic, and immunologic features of IgA pemphigus.
METHODS
We performed a systematic review using MEDLINE, Embase, and Web of Science databases. Case reports and series of patients with IgA pemphigus were included.
RESULTS
A total of 119 eligible studies, comprising 137 patients with IgA pemphigus with a mean age of 51.5 ± 21.0 years, were included. Most patients presented with vesicles (80.8%), pustules (75.0%), and circinate plaques (63.6%). Pruritus was present in 65.6% of reported patients. Intercellular deposition of IgA was noted in almost all patients (97.0%), and the remaining 3.0% of patients had IgA positivity on indirect immunofluorescence or enzyme-linked immunosorbent assay confirming the diagnosis. IgA circulating intercellular antibodies were detected in only 66.7% patients. IgA gammopathy and ulcerative colitis were associated with IgA pemphigus in 9.5% and 6.6% patients, respectively. Oral dapsone and corticosteroids were the mostly commonly used treatments.
LIMITATIONS
Results are mainly based on case reports and small case series.
CONCLUSIONS
The diagnosis of IgA pemphigus may be considered in patients presenting with vesiculopustular eruption and circinate plaques with truncal and extremity involvement.
Topics: Adult; Aged; Humans; Immunoglobulin A; Middle Aged; Pemphigus
PubMed: 31812619
DOI: 10.1016/j.jaad.2019.11.059 -
European Journal of Nuclear Medicine... Dec 2023The current clinical recommendations posit the deployment of specific approved radiolabeled prostate-specific membrane antigen-ligand positron emission tomography (PSMA... (Meta-Analysis)
Meta-Analysis Review
The diagnostic accuracy of radiolabeled PSMA-ligand PET for tumour staging in newly diagnosed prostate cancer patients compared to histopathology: a systematic review and meta-analysis.
PURPOSE
The current clinical recommendations posit the deployment of specific approved radiolabeled prostate-specific membrane antigen-ligand positron emission tomography (PSMA PET) for detecting metastatic prostate cancer during primary staging. Nevertheless, the precise efficacy of such ligands in localizing intraprostatic tumours (index tumour) and T-staging is not well established. Consequently, the objective of this inquiry is to ascertain the diagnostic accuracy of PSMA-PET in the tumour staging of newly diagnosed prostate cancer by means of a meta-analysis that integrates studies utilizing histological confirmation as the reference standard.
METHODS
In this study, we conducted a systematic literature search of the PubMed, Embase, Web of Science, and Cochrane Library databases using a predefined collection of search terms. These terms included 'PSMA PET', 'primary staging', and 'prostate cancer'. Subsequently, two independent reviewers evaluated all the studies based on predetermined inclusion criteria, extracted pertinent data, and assessed the quality of evidence. Any disparities were resolved by a third reviewer. A random effects Sidik-Jonkman model was applied to conduct a meta-analysis and estimate the diagnostic accuracy on a per-patient basis, along with 95% confidence intervals. Moreover, an appraisal regarding the likelihood of publication bias and the impact of small-study effects was performed utilizing both Egger's test and a graphical examination of the funnel plot.
RESULTS
The present analysis comprised a total of twenty-three scientific papers encompassing 969 patients and involved their analysis by both qualitative and quantitative approaches. The results of this study demonstrated that the estimated diagnostic accuracy of PSMA PET/CT and PSMA PET/MRI, for the detection of intraprostatic tumours, regardless of the type of PSMA-ligand, was 86% (95% CI: 76-96%) and 97% (95% CI: 94-100%), respectively. Furthermore, the diagnostic accuracy for the detection of extraprostatic extension (EPE) was 73% (95% CI: 64-82%) and 77% (95% CI: 69-85%), while the diagnostic accuracy for the detection of seminal vesicle involvement (SVI) was 87% (95% CI: 80-93) and 90% (95% CI: 82-99%), respectively.
CONCLUSION
The present investigation has demonstrated that PSMA PET/MRI surpasses currently recommended multiparametric magnetic resonance imaging (mpMRI) in terms of diagnostic accuracy as inferred from a notable data trajectory, whereas PSMA-PET/CT exhibited comparable diagnostic accuracy for intraprostatic tumour detection and T-staging compared to mpMRI. Nevertheless, the analysis has identified certain potential limitations, such as small-study effects and a potential for publication bias, which may impact the overall conclusions drawn from this study.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Neoplasm Staging; Ligands; Gallium Radioisotopes; Prostatic Neoplasms; Positron-Emission Tomography
PubMed: 37597010
DOI: 10.1007/s00259-023-06392-0 -
Journal of Endourology Oct 2023Numerous continence-sparing radical prostatectomy techniques have been developed to enhance postoperative early continence (EC) recovery; however, evidence regarding...
Numerous continence-sparing radical prostatectomy techniques have been developed to enhance postoperative early continence (EC) recovery; however, evidence regarding the best approach remains controversial. The objectives are to provide a critical appraisal of various prostatectomy techniques, based on the evidence of quality-assessed randomized control trials (RCTs); to summarize the immediate continence and the EC reported; and to propose a new standardization for continence outcomes reporting. Data acquired from five medical registries were reported to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Evidence from published, English, full-text RCTs reporting postoperative urinary continence outcomes within 6 months from surgery was included. The heterogeneity of surgical techniques and continence definitions did not allow a meta-analysis. All RCTs were critically appraised, and quality assessed. In total, 39 RCTs were included: 19 of 39 studies were low-quality RCTs, presenting small cohort, monocentric, or single-surgeon data. The best RCT-supported evidence is in favor of robot-assisted radical prostatectomy (RARP) compared with laparoscopic radical prostatectomy (LRP) and of the Retzius-sparing (RS) technique over the traditional prostatectomy. Other techniques such as bladder neck and puboprostatic ligament (PPL) preservation, posterior reconstruction with or without combination of anterior suspension technique, and nerve-sparing (NS) approach seem to enhance EC. Oppositely, the endopelvic fascia preservation, bladder neck mucosa eversion/plication/slings, and the selective ligature of dorsal venous complex (DVC) were not significantly associated with EC improvements. RCTs are lacking on pubovesical complex-sparing, seminal vesicle preservation, anterior reconstruction of the puboprostatic collar, musculofascial reconstruction, and DVC suspension to the periosteum of the pubic bone techniques. RARP and RS have high-quality evidence supporting their ability to enhance postoperative EC recovery. NS, bladder neck, and PPL preservation may contribute to better EC recovery, although the evidence level is low. Further multicenter RCTs are needed to establish the optimal combination of standard surgical techniques. A new continence outcome-reporting standardization was proposed.
PubMed: 37597197
DOI: 10.1089/end.2023.0188 -
International Journal of Molecular... Aug 2023The use of platelet-rich plasma (PRP) has gained increasing interest in recent decades. The platelet secretome contains a multitude of growth factors, cytokines,... (Review)
Review
The use of platelet-rich plasma (PRP) has gained increasing interest in recent decades. The platelet secretome contains a multitude of growth factors, cytokines, chemokines, and other biological biomolecules. In recent years, developments in the field of platelets have led to new insights, and attention has been focused on the platelets' released extracellular vesicles (EVs) and their role in intercellular communication. In this context, the aim of this review was to compile the current evidence on PRP-derived extracellular vesicles to identify the advantages and limitations fortheir use in the upcoming clinical applications. A total of 172 articles were identified during the systematic literature search through two databases (PubMed and Web of Science). Twenty publications met the inclusion criteria and were included in this review. According to the results, the use of PRP-EVs in the clinic is an emerging field of great interest that represents a promising therapeutic option, as their efficacy has been demonstrated in the majority of fields of applications included in this review. However, the lack of standardization along the procedures in both the field of PRP and the EVs makes it extremely challenging to compare results among studies. Establishing standardized conditions to ensure optimized and detailed protocols and define parameters such as the dose or the EV origin is therefore urgent. Further studies to elucidate the real contribution of EVs to PRP in terms of composition and functionality should also be performed. Nevertheless, research on the field provides promising results and a novel basis to deal with the regenerative medicine and drug delivery fields in the future.
Topics: Blood Platelets; Cell Communication; Extracellular Vesicles; Platelet-Rich Plasma; Regenerative Medicine
PubMed: 37685849
DOI: 10.3390/ijms241713043 -
Stem Cells Translational Medicine Sep 2021Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this... (Meta-Analysis)
Meta-Analysis Review
Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this systematic review and meta-analysis summarized the effect of cell-based interventions in DKD animal models and treatment-related factors modifying outcomes. Electronic databases were searched for original investigations applying cell-based therapy in diabetic animals with kidney endpoints (January 1998-May 2019). Weighted or standardized mean differences were estimated for kidney outcomes and pooled using random-effects models. Subgroup analyses tested treatment-related factor effects for outcomes (creatinine, urea, urine protein, fibrosis, and inflammation). In 40 studies (992 diabetic rodents), therapy included mesenchymal stem/stromal cells (MSC; 61%), umbilical cord/amniotic fluid cells (UC/AF; 15%), non-MSC (15%), and cell-derived products (13%). Tissue sources included bone marrow (BM; 65%), UC/AF (15%), adipose (9%), and others (11%). Cell-based therapy significantly improved kidney function while reducing injury markers (proteinuria, histology, fibrosis, inflammation, apoptosis, epithelial-mesenchymal-transition, oxidative stress). Preconditioning, xenotransplantation, and disease-source approaches were effective. MSC and UC/AF cells had greater effect on kidney function while cell products improved fibrosis. BM and UC/AF tissue sources more effectively improved kidney function and proteinuria vs adipose or other tissues. Cell dose, frequency, and administration route also imparted different benefits. In conclusion, cell-based interventions in diabetic animals improved kidney function and reduced injury with treatment-related factors modifying these effects. These findings may aid in development of optimal repair strategies through selective use of cells/products, tissue sources, and dose administrations to allow for successful adaptation of this novel therapeutic in human DKD.
Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Fibrosis; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Umbilical Cord
PubMed: 34106528
DOI: 10.1002/sctm.19-0419 -
International Journal of Molecular... Sep 2022The pathophysiology of chronic rhinosinusitis (CRS) is multifactorial and not entirely clear. The objective of the review was to examine the current state of knowledge... (Review)
Review
The pathophysiology of chronic rhinosinusitis (CRS) is multifactorial and not entirely clear. The objective of the review was to examine the current state of knowledge concerning the role of exosomes in CRS. For this systematic review, we searched PubMed/MEDLINE, Scopus, CENTRAL, and Web of Science databases for studies published until 7 August 2022. Only original research articles describing studies published in English were included. Reviews, book chapters, case studies, conference papers, and opinions were excluded. The quality of the evidence was assessed with the modified Office and Health Assessment and Translation (OHAT) Risk of Bias Rating Tool for Human and Animal Studies. Of 250 records identified, 17 were eligible, all of which had a low to moderate risk of overall bias. Presented findings indicate that exosomal biomarkers, including proteins and microRNA, act as promising biomarkers in the diagnostics and prognosis of CRS patients and, in addition, may contribute to finding novel therapeutic targets. Exosomes reflecting tissue proteomes are excellent, highly available material for studying proteomic alterations noninvasively. The first steps have already been taken, but more advanced research on nasal exosomes is needed, which might open a wider door for individualized medicine in CRS.
Topics: Animals; Biomarkers; Chronic Disease; Exosomes; Humans; MicroRNAs; Proteome; Proteomics; Rhinitis; Sinusitis
PubMed: 36232588
DOI: 10.3390/ijms231911284 -
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 -
Journal of Nanobiotechnology Oct 2023This systematic review and meta-analysis aimed to evaluate the efficacy of engineered extracellular vesicles (EEVs) in the treatment of ischemic stroke (IS) in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis aimed to evaluate the efficacy of engineered extracellular vesicles (EEVs) in the treatment of ischemic stroke (IS) in preclinical studies and to compare them with natural extracellular vesicles (EVs). The systematic review provides an up-to-date overview of the current state of the literature on the use of EEVs for IS and informs future research in this area.
METHODS
We searched PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases for peer-reviewed preclinical studies on the therapeutic effect of EEVs on IS.Databases ranged from the inception to August 1, 2023. The outcome measures included infarct volumes, neurological scores, behavioral scores, apoptosis rates, numbers of neurons, and levels of IL-1β, IL-6, and TNF-α. The CAMARADES checklist was used to assess the quality and bias risks of the studies. All statistical analyses were performed using RevMan 5.4 software.
RESULTS
A total of 28 studies involving 1760 animals met the inclusion criteria. The results of the meta-analysis showed that compared to natural EVs, EEVs reduced infarct volume (percentage: SMD = -2.33, 95% CI: -2.92, -1.73; size: SMD = -2.36, 95% CI: -4.09, -0.63), improved neurological scores (mNSS: SMD = -1.78, 95% CI: -2.39, -1.17; Zea Longa: SMD = -2.75, 95% CI: -3.79, -1.71), promoted behavioral recovery (rotarod test: SMD = 2.50, 95% CI: 1.81, 3.18; grid-walking test: SMD = -3.45, 95% CI: -5.15, -1.75; adhesive removal test: SMD = -2.60, 95% CI: -4.27, -0.93; morris water maze test: SMD = -3.91, 95% CI: -7.03, -0.79), and reduced the release of proinflammatory factors (IL-1β: SMD = -2.02, 95% CI: -2.77, -1.27; IL-6: SMD = -3.01, 95% CI: -4.47, -1.55; TNF-α: SMD = -2.72, 95% CI: -4.30, -1.13), increasing the number of neurons (apoptosis rate: SMD = -2.24, 95% CI: -3.32, -1.16; the number of neurons: SMD = 3.70, 95% CI: 2.44, 4.96). The funnel plots for the two main outcome measures were asymmetric, indicating publication bias. The median score on the CAMARADES checklist was 7 points (IQR: 6-9).
CONCLUSIONS
This meta-analysis shows that EEVs are superior to natural EVs for the treatment of IS. However, research in this field is still at an early stage, and more research is needed to fully understand the potential therapeutic mechanism of EEVs and their potential use in the treatment of IS.
PROSPERO REGISTRATION NUMBER
CRD42022368744.
Topics: Animals; Ischemic Stroke; Interleukin-6; Tumor Necrosis Factor-alpha; Extracellular Vesicles; Infarction
PubMed: 37904204
DOI: 10.1186/s12951-023-02114-8 -
Stem Cell Research & Therapy Jun 2022Primary Sjögren's syndrome (pSS) is a diffuse connective tissue disease characterized by the invasion of exocrine glands such as lacrimal and salivary glands, abnormal... (Review)
Review
Primary Sjögren's syndrome (pSS) is a diffuse connective tissue disease characterized by the invasion of exocrine glands such as lacrimal and salivary glands, abnormal proliferation of T and B lymphocytes, and infiltration of tissue lymphocytes. With the development of modern medicine, although research on the pathogenesis, diagnosis, and treatment of pSS has made significant progress, its pathogenesis has not been fully understood. Meanwhile, in the era of individualized treatment, it remains essential to further explore early diagnosis and treatment methods. Exosomes, small vesicles containing proteins and nucleic acids, are a subtype of extracellular vesicles secreted by various cells and present in various body fluids. Exosomes contribute to a variety of biological functions, including intercellular signal transduction and pathophysiological processes, and may play a role in immune tolerance. Therefore, exosomes are key to understanding the pathogenesis of diseases. Exosomes can also be used as a therapeutic tool for pSS because of their biodegradability, low immunogenicity and toxicity, and the ability to bypass the blood-brain barrier, implying the prospect of a broad application in the context of pSS. Here, we systematically review the isolation, identification, tracing, and mode of action of extracellular vesicles, especially exosomes, as well as the research progress in the pathogenesis, diagnosis, and treatment of pSS.
Topics: B-Lymphocytes; Exosomes; Extracellular Vesicles; Humans; Salivary Glands; Sjogren's Syndrome
PubMed: 35659085
DOI: 10.1186/s13287-022-02912-1