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Journal of Personalized Medicine Dec 2023Alongside their long-term effects, post-concussion syndrome (PCS) and mild traumatic brain injuries (mTBI) are significant public health concerns. Currently, there is a... (Review)
Review
BACKGROUND
Alongside their long-term effects, post-concussion syndrome (PCS) and mild traumatic brain injuries (mTBI) are significant public health concerns. Currently, there is a lack of reliable biomarkers for diagnosing and monitoring mTBI and PCS. Exosomes are small extracellular vesicles secreted by cells that have recently emerged as a potential source of biomarkers for mTBI and PCS due to their ability to cross the blood-brain barrier and reflect the pathophysiology of brain injury. In this study, we aimed to investigate the role of salivary exosomal biomarkers in mTBI and PCS.
METHODS
A systematic review using the PRISMA guidelines was conducted, and studies were selected based on their relevance to the topic.
RESULTS
The analyzed studies have shown that exosomal tau, phosphorylated tau (p-tau), amyloid beta (Aβ), and microRNAs (miRNAs) are potential biomarkers for mTBI and PCS. Specifically, elevated levels of exosomal tau and p-tau have been associated with mTBI and PCS as well as repetitive mTBI. Dysregulated exosomal miRNAs have also been observed in individuals with mTBI and PCS. Additionally, exosomal Prion cellular protein (PRPc), coagulation factor XIII (XIIIa), synaptogyrin-3, IL-6, and aquaporins have been identified as promising biomarkers for mTBI and PCS.
CONCLUSION
Salivary exosomal biomarkers have the potential to serve as non-invasive and easily accessible diagnostic and prognostic tools for mTBI and PCS. Further studies are needed to validate these biomarkers and develop standardized protocols for their use in clinical settings. Salivary exosomal biomarkers can improve the diagnosis, monitoring, and treatment of mTBI and PCS, leading to improved patient outcomes.
PubMed: 38248736
DOI: 10.3390/jpm14010035 -
Journal of Nanobiotechnology Jan 2024Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins,... (Review)
Review
Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins, lipids, and nucleic acids. Engineered exosomes generated through genetic modification of parent cells show promise as drug delivery vehicles, and they have been demonstrated to have great therapeutic potential for treating cancer, cardiovascular, neurological, and immune diseases, but systematic knowledge is lacking regarding optimization of drug loading and assessment of delivery efficacy. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, and current techniques for assessing exosome drug loading and release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes are critically examined. Additionally, this review synthesizes the latest applications of exosome engineering and drug delivery in clinical translation. The knowledge compiled in this review provides a framework for the rational design and rigorous assessment of exosomes as therapeutics. Continued advancement of robust characterization methods and reporting standards will accelerate the development of exosome engineering technologies and pave the way for clinical studies.
Topics: Humans; Exosomes; Tissue Distribution; Drug Delivery Systems; Extracellular Vesicles; Neoplasms; Pharmaceutical Preparations
PubMed: 38172932
DOI: 10.1186/s12951-023-02259-6 -
Journal of Plastic, Reconstructive &... Jan 2024Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic dermatosis that can develop at a surgical site. Diagnosis can be challenging at its presentation causing... (Review)
Review
BACKGROUND
Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic dermatosis that can develop at a surgical site. Diagnosis can be challenging at its presentation causing delays in appropriate treatment. The aim of this study is to review the current literature as well as to describe the clinical presentation, diagnostic pathway, and treatment of PG after reduction mammaplasty in order to define a standardized multidisciplinary diagnostic and therapeutic approach. In the future, this may ease early identification and prompt treatment, and eventually minimize severe morbidity and long-term sequelae.
METHODS
The entire PubMed/Medline database was screened following the PRISMA guidelines to identify studies describing PG that have occurred after reduction mammoplasty.
RESULTS
Twenty-eight articles including 31 patients reported a PG after breast reduction surgery between January 1988 and March 2022. Twenty-one (68%) patients presented with skin ulcerations, 14 (45%) with erythema, and 5 (16%) with vesicles. Out of the 30 cases that underwent bilateral surgery, 18 (60%) developed PG bilaterally. In 12 out of 31 patients, nipple-areolar complex (NAC) involvement was evaluated, though in 10 patients (83%) the NAC was spared. Of the 20 patients (65%) who underwent skin biopsies for histopathological examination, 18 (90%) showed neutrophilic infiltration of the dermal layers. All 31 patients (100%) showed rapid clinical improvement after the introduction of immunosuppressive therapy.
CONCLUSIONS
PG can result in devastating skin alterations also after reduction mammoplasty, if misdiagnosed. However, it presents with constant yet unspecific local and general signs and symptoms that can be recognized to early initiate an appropriate pharmacological treatment.
Topics: Female; Humans; Pyoderma Gangrenosum; Mammaplasty; Skin; Mastectomy; Immunosuppression Therapy
PubMed: 38118291
DOI: 10.1016/j.bjps.2023.11.041 -
Journal of Neurology Apr 2024Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS), exhibit overlapping early-stage symptoms, complicating definitive diagnosis despite heterogeneous cellular and regional pathophysiology. Additionally, the progression and the eventual conversion of prodromal conditions such as REM behavior disorder (RBD) to PD, MSA, or DLB remain challenging to predict. Extracellular vesicles (EVs) are small, membrane-enclosed structures released by cells, playing a vital role in communicating cell-state-specific messages. Due to their ability to cross the blood-brain barrier into the peripheral circulation, measuring biomarkers in blood-isolated speculative CNS enriched EVs has become a popular diagnostic approach. However, replication and independent validation remain challenging in this field. Here, we aimed to evaluate the diagnostic accuracy of speculative CNS-enriched EVs for parkinsonian disorders.
METHODS
We conducted a PRISMA-guided systematic review and meta-analysis, covering 18 studies with a total of 1695 patients with PD, 253 with MSA, 21 with DLB, 172 with PSP, 152 with CBS, 189 with RBD, and 1288 HCs, employing either hierarchical bivariate models or univariate models based on study size.
RESULTS
Diagnostic accuracy was moderate for differentiating patients with PD from HCs, but revealed high heterogeneity and significant publication bias, suggesting an inflation of the perceived diagnostic effectiveness. The bias observed indicates that studies with non-significant or lower effect sizes were less likely to be published. Although results for differentiating patients with PD from those with MSA or PSP and CBS appeared promising, their validity is limited due to the small number of involved studies coming from the same research group. Despite initial reports, our analyses suggest that using speculative CNS-enriched EV biomarkers may not reliably differentiate patients with MSA from HCs or patients with RBD from HCs, due to their lesser accuracy and substantial variability among the studies, further complicated by substantial publication bias.
CONCLUSION
Our findings underscore the moderate, yet unreliable diagnostic accuracy of biomarkers in speculative CNS-enriched EVs in differentiating parkinsonian disorders, highlighting the presence of substantial heterogeneity and significant publication bias. These observations reinforce the need for larger, more standardized, and unbiased studies to validate the utility of these biomarkers but also call for the development of better biomarkers for parkinsonian disorders.
Topics: Humans; Parkinsonian Disorders; Parkinson Disease; Multiple System Atrophy; Supranuclear Palsy, Progressive; REM Sleep Behavior Disorder; Biomarkers; Extracellular Vesicles; Diagnosis, Differential
PubMed: 38103086
DOI: 10.1007/s00415-023-12093-3 -
Frontiers in Oncology 2023Prostate cancer is viewed as the second most common cancer in men worldwide. In our study, we used bibliometric analysis to construct a visual map of the relationship...
BACKGROUND
Prostate cancer is viewed as the second most common cancer in men worldwide. In our study, we used bibliometric analysis to construct a visual map of the relationship between prostate cancer and exosomes with the intent of uncovering research trends and current hotspots in this field.
METHOD
We searched the Web of Science Core Collection for all publications in the prostate cancer associated with exosome field came out since 2010. With the assistance of bibliometric analysis software such as VOSviewer and CiteSpace, we conducted data extraction and analysis for countries/regions, institutions, authors, journals, references and keywords.
RESULTS
A bibliometric analysis of 990 publications was performed. Since 2010, the published quantity and cited frequency of the prostate cancer-associated exosome field have revealed an increasing tendency. In this field, we visualized the research trends by the means of analyzing the references and keywords. We obtained the statistical data: the total citations of publications have increased to 55,462, the average citation per article has reached 55.3 times, and the H-index has amounted to 110. Our findings supported that USA, China and Italy rank the top countries with both the maximum publications and strongest cooperations. Harvard Medical School, Cedars Sinai Med Ctr, Johns Hopkins University, are top institutions in the center of research as they are held to be. Thery C, Skog J and Taylor DD are the leading and outstanding professors and researchers. And top journals like Prostate, Plos One and Journal of Extracellular Vesicle expressed keen interests in this field. Based on our analysis and research, we believe that this field is attracting more and more attention and will focus on tumor bone metastasis, drug delivery, and tumor suppressor.
CONCLUSION
In the past 12 years, researchers have dedicated their efforts to prostate cancer associated exosome. On the basis of previous studies, scientists are showing increasingly solicitude for the role of exosome in prostate cancer progression and potential therapy such as drug delivery.
PubMed: 38090502
DOI: 10.3389/fonc.2023.1270104 -
Journal of Alzheimer's Disease : JAD 2024A key aspect of synaptic dysfunction in Alzheimer's disease (AD) is loss of synaptic proteins. Previous publications showed that the presynaptic machinery is more... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A key aspect of synaptic dysfunction in Alzheimer's disease (AD) is loss of synaptic proteins. Previous publications showed that the presynaptic machinery is more strongly affected than postsynaptic proteins. However, it has also been reported that presynaptic protein loss is highly variable and shows region- and protein-specificity.
OBJECTIVE
The objective of this meta-analysis was to provide an update on the available literature and to further characterize patterns of presynaptic protein loss in AD.
METHODS
Systematic literature search was conducted for studies published between 2015-2022 which quantified presynaptic proteins in postmortem tissue from AD patients and healthy controls. Three-level random effects meta-analyses of twenty-two identified studies was performed to characterize overall presynaptic protein loss and changes in specific regions, proteins, protein families, and functional categories.
RESULTS
Meta-analysis confirmed overall loss of presynaptic proteins in AD patients. Subgroup analysis revealed region specificity of protein loss, with largest effects in temporal and frontal cortex. Results concerning different groups of proteins were also highly variable. Strongest and most consistently affected was the family of synaptosome associated proteins, especially SNAP25. Among the most severely affected were proteins regulating dense core vesicle exocytosis and the synaptic vesicle cycle.
CONCLUSIONS
Results confirm previous literature related to presynaptic protein loss in AD patients and provide further in-depth characterization of most affected proteins and presynaptic functions.
Topics: Humans; Alzheimer Disease; Proteins; Presynaptic Terminals
PubMed: 38073390
DOI: 10.3233/JAD-231034 -
Stem Cells (Dayton, Ohio) Mar 2024The high prevalence and complex etiology of renal diseases already impose a heavy disease burden on patients and society. In certain kidney diseases such as acute kidney... (Review)
Review
The high prevalence and complex etiology of renal diseases already impose a heavy disease burden on patients and society. In certain kidney diseases such as acute kidney injury and chronic kidney disease, current treatments are limited to slowing rather than stabilizing or reversing disease progression. Therefore, it is crucial to study the pathological mechanisms of kidney disease and discover new therapeutic targets and effective therapeutic drugs. As cell-free therapeutic strategies are continually being developed, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have emerged as a hot topic for research in the field of renal diseases. Studies have demonstrated that MSC-EVs not only reproduce the therapeutic effects of MSCs but also localize to damaged kidney tissue. Compared to MSCs, MSC-EVs have several advantages, including ease of preservation, low immunogenicity, an inability to directly form tumors, and ease of artificial modification. Exploring the detailed mechanisms of MSC-EVs by developing standardized culture, isolation, purification, and drug delivery strategies will help facilitate their clinical application in kidney diseases. Here, we provide a comprehensive overview of studies about MSC-EVs in kidney diseases and discuss their limitations at the human nephrology level.
Topics: Humans; Extracellular Vesicles; Kidney; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Renal Insufficiency, Chronic
PubMed: 38035715
DOI: 10.1093/stmcls/sxad089 -
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 -
International Journal of Molecular... Oct 2023Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer "theranostic" tools, with strong clinical relevance....
Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer "theranostic" tools, with strong clinical relevance. Although their potential in breast cancer diagnosis has been widely reported, further studies are still required to address this challenging issue. The present study examined the expression profiles of EV-packaged miRNAs to identify novel miRNA signatures in breast cancer and verified their diagnostic accuracy. Circulating EVs were isolated from healthy controls and breast cancer patients and characterized following the MISEV 2018 guidelines. RNA-sequencing and real-time PCR showed that miRNA-27a and miRNA-128 were significantly down-regulated in patient-derived EVs compared to controls in screening and validation cohorts. Bioinformatics analyses of miRNA-target genes indicated several enriched biological processes/pathways related to breast cancer. Receiver operating characteristic (ROC) curves highlighted the ability of these EV-miRNAs to distinguish breast cancer patients from non-cancer controls. According to other reports, the levels of EV-miRNA-27a and EV-miRNA-128 are not associated with their circulating ones. Finally, evidence from the studies included in our systematic review underscores how the expression of these miRNAs in biofluids is still underinvestigated. Our findings unraveled the role of serum EV-derived miRNA-27a and miRNA-128 in breast cancer, encouraging further investigation of these two miRNAs within EVs towards improved breast cancer detection.
Topics: Humans; Female; MicroRNAs; Breast Neoplasms; Extracellular Vesicles
PubMed: 37958677
DOI: 10.3390/ijms242115695 -
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