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Journal of Extracellular Vesicles Aug 2020Severe COVID-19 infection results in bilateral interstitial pneumonia, often leading to acute respiratory distress syndrome (ARDS) and pulmonary fibrosis in survivors.... (Review)
Review
Severe COVID-19 infection results in bilateral interstitial pneumonia, often leading to acute respiratory distress syndrome (ARDS) and pulmonary fibrosis in survivors. Most patients with severe COVID-19 infections who died had developed ARDS. Currently, ARDS is treated with supportive measures, but regenerative medicine approaches including extracellular vesicle (EV)-based therapies have shown promise. Herein, we aimed to analyse whether EV-based therapies could be effective in treating severe pulmonary conditions that affect COVID-19 patients and to understand their relevance for an eventual therapeutic application to human patients. Using a defined search strategy, we conducted a systematic review of the literature and found 39 articles (2014-2020) that reported effects of EVs, mainly derived from stem cells, in lung injury models (one large animal study, none in human). EV treatment resulted in: (1) attenuation of inflammation (reduction of pro-inflammatory cytokines and neutrophil infiltration, M2 macrophage polarization); (2) regeneration of alveolar epithelium (decreased apoptosis and stimulation of surfactant production); (3) repair of microvascular permeability (increased endothelial cell junction proteins); (4) prevention of fibrosis (reduced fibrin production). These effects were mediated by the release of EV cargo and identified factors including miRs-126, -30b-3p, -145, -27a-3p, syndecan-1, hepatocyte growth factor and angiopoietin-1. This review indicates that EV-based therapies hold great potential for COVID-19 related lung injuries as they target multiple pathways and enhance tissue regeneration. However, before translating EV therapies into human clinical trials, efforts should be directed at developing good manufacturing practice solutions for EVs and testing optimal dosage and administration route in large animal models.
PubMed: 32944185
DOI: 10.1080/20013078.2020.1795365 -
Stem Cells Translational Medicine Jul 2022Mesenchymal stromal cells (MSCs) may reduce mortality in patients with COVID-19; however, early evidence is based on few studies with marked interstudy heterogeneity.... (Meta-Analysis)
Meta-Analysis
Updated Living Systematic Review and Meta-analysis of Controlled Trials of Mesenchymal Stromal Cells to Treat COVID-19: A Framework for Accelerated Synthesis of Trial Evidence for Rapid Approval-FASTER Approval.
BACKGROUND
Mesenchymal stromal cells (MSCs) may reduce mortality in patients with COVID-19; however, early evidence is based on few studies with marked interstudy heterogeneity. The second iteration of our living systematic review and meta-analysis evaluates a framework needed for synthesizing evidence from high-quality studies to accelerate consideration for approval.
METHODS
A systematic search of the literature was conducted on November 15, 2021, to identify all English-language, full-text, and controlled clinical studies examining MSCs to treat COVID-19 (PROSPERO: CRD42021225431).
FINDINGS
Eleven studies were identified (403 patients with severe and/or critical COVID-19, including 207 given MSCs and 196 controls). All 11 studies reported mortality and were pooled through random-effects meta-analysis. MSCs decreased relative risk of death at study endpoint (RR: 0.50 [95% CI, 0.34-0.75]) and RR of death at 28 days after treatment (0.19 [95% CI], 0.05-0.78) compared to controls. MSCs also decreased length of hospital stay (mean difference (MD: -3.97 days [95% CI, -6.09 to -1.85], n = 5 studies) and increased oxygenation levels at study endpoint compared to controls (MD: 105.62 mmHg O2 [95% CI, 73.9-137.3,], n = 3 studies). Only 2 of 11 studies reported on all International Society for Cellular Therapy (ISCT) criteria for MSC characterization. Included randomized controlled trials were found to have some concerns (n = 2) to low (n = 4) risk of bias (RoB), while all non-randomized studies were found to have moderate (n = 5) RoB.
INTERPRETATION
Our updated living systematic review concludes that MSCs can likely reduce mortality in patients with severe or critical COVID-19. A master protocol based on our Faster Approval framework appears necessary to facilitate the more accelerated accumulation of high-quality evidence that would reduce RoB, improve consistency in product characterization, and standardize outcome reporting.
Topics: Bias; COVID-19; Humans; Lung; Mesenchymal Stem Cells; Randomized Controlled Trials as Topic
PubMed: 35758400
DOI: 10.1093/stcltm/szac038 -
International Journal of Molecular... Apr 2022Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular... (Review)
Review
Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular biomarkers have gained more and more importance both in the diagnosis and therapy of glial tumors. At the same time, it has become clear that non neoplastic cells, which constitute about 30% of glioma mass, dramatically influence tumor growth, spread, and recurrence. This is the main reason why, in recent years, scientific research has been focused on understanding the function and the composition of tumor microenvironment and its role in gliomagenesis and recurrence. The aim of this review is to summarize the most recent discovery about resident microglia, tumor-associated macrophages, lymphocytes, and the role of extracellular vesicles and their bijective interaction with glioma cells. Moreover, we reported the most recent updates about new therapeutic strategies targeting immune system receptors and soluble factors. Understanding how glioma cells interact with non-neoplastic cells in tumor microenvironment is an essential step to comprehend mechanisms at the base of disease progression and to find new therapeutic strategies for GBM patients. However, no significant results have yet been obtained in studies targeting single molecules/pathways; considering the complex microenvironment, it is likely that only by using multiple therapeutic agents acting on multiple molecular targets can significant results be achieved.
Topics: Brain Neoplasms; Glioblastoma; Glioma; Humans; Macrophages; Microglia; Tumor Microenvironment
PubMed: 35456984
DOI: 10.3390/ijms23084166 -
Iranian Journal of Reproductive Medicine Mar 2015Antibiotic therapies used in treatment of many diseases have adverse effects on fertility. This review analyzes previous comparative studies that surveyed the effects of... (Review)
Review
BACKGROUND
Antibiotic therapies used in treatment of many diseases have adverse effects on fertility. This review analyzes previous comparative studies that surveyed the effects of two common groups of antibiotics on male fertility.
OBJECTIVE
To evaluate histo-pathological effects of fluoroquinolones and aminoglycosides on sperm parameters and male reproductive tissue.
MATERIALS AND METHODS
Articles about the effects of aminoglycosides and fluoroquinolones on male infertility, sperm parameters, male reproductive tissue, and spermatogenesis in English and Persian languages published on Google Scholar and PubMed databases from January 2000 to December 2013 were assessed. Randomized controlled trials (RCTs) assessing the effects of aminoglycosides or fluoroquinolones on sperm parameters, artificial insemination, and male reproductive tract or RCTs comparing aminoglycosides vs. fluoroquinolones were eligible for inclusion. For ascertaining the reliability of study, data were extracted independently and in duplicate by two investigators.
RESULTS
Sperm viability was decreased significantly with streptomycin, gentamicin, and neomycin (p<0.001). Sperm motility was decreased significantly with gentamicin and neomycin (p<0.05). Total sperm count was significantly decreased with ofloxacin, gentamicin, streptomycin, and neomycin (p<0.022). There was significant decrease in post-thawing motility with low dose and high dose of ciprofloxacin. Testis weight was decreased with gentamicin and ofloxacin significantly (p<0.011). There was significant decrease in seminal vesicle weight with gentamicin, neomycin, and ofloxacin (p<0.022). Furthermore, changes in epididymis weight, percentage of total apoptotic cells, and diameter of seminiferous tubule were significant with all drugs including streptomycin, gentamicin, neomycin, and ofloxacin (p<0.05).
CONCLUSION
Streptomycin has less negative effects on cell's apoptosis and sperm parameters as compared to other drugs. Gentamicin has more detrimental effects so lesser dosage and duration is recommended. Fluoroquinolones showed negative effects on testis tissue and sperm parameters. Ciprofloxacin has less adverse effects than gentamicin in artificial insemination.
PubMed: 26000002
DOI: No ID Found -
Frontiers in Medicine 2022Infections in the male genitourinary system with bacterial and viral agents may play a significant role in male infertility. These agents usually infect the urethra,...
OBJECTIVES
Infections in the male genitourinary system with bacterial and viral agents may play a significant role in male infertility. These agents usually infect the urethra, seminal vesicles, prostate, epididymis, vas deferens, and testes retrograde through the reproductive system. A meta-analysis review study was performed to evaluate the presence of bacterial and viral agents in the semen of infertile men and its correlation with infertility.
METHODS
Relevant cross-sectional and/or case-control studies were found by an online review of national and international databases (Web of Science, PubMed, Scopus, Science Direct, and Google scholar), and suitable studies were selected. A checklist determined the qualities of all studies. Heterogeneity assay among the primary studies was evaluated by Cochran's test and I index (significance level 50%). A statistical analysis was conducted using the Comprehensive Stata ver. 14 package (StataCorp, College Station, TX, United States).
RESULTS
Seventy-two studies were included in this meta-analysis. Publication bias was compared with Egger's test, and the impact of each research on overall estimate was evaluated by sensitivity analysis. In 56 studies, the rate of bacterial infections in the semen of infertile men was 12% [95% confidence interval (CI): 10-13]. Also, in 26 case-control studies, the association of infertility in men with bacterial infections was evaluated. The results show that the odds ratio of infertility in men exposed to bacterial infections is 3.31 times higher than that in non-infected men (95% CI: 2.60-4.23). Besides, in 9 studies that examined the prevalence of human papillomavirus (HPV), herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), and herpes simplex virus 1-2 (HSV1-2) in infertile men, the frequency of these viruses was 15% (95% CI: 9-21). In 6 case-control studies, the association between human cytomegalovirus (HCMV), Cytomegalovirus (CMV), and HPV and male infertility was evaluated. The chance of male infertility due to exposure to these viruses was 2.24 times higher than those without exposure to these viruses (CI 95%: 1.9-4.52). The results show that the chance of infertility in men exposed to bacteria was significantly higher than that in the uninfected population.
CONCLUSION
This meta-analysis showed that viral and bacterial infections are a risk factor and could impair male fertility potential. Moreover, our study supports the hypothesis that bacterial and viral infections of the genital tract correlate positively with impairment of sperm quality in the male population.
PubMed: 35602502
DOI: 10.3389/fmed.2022.835254 -
International Journal of Molecular... May 2023Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their... (Review)
Review
Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their translation and/or stability. MiRNAs regulate nearly all cellular functions, including the cell fate of mesenchymal stromal cells (MSCs). It is now accepted that various pathologies arise at the stem level, and, in this scenario, the role played by miRNAs in the fate of MSCs becomes of primary concern. Here we have considered the existing literature in the field of miRNAs, MSCs and skin diseases, classified as inflammatory (such as psoriasis and atopic dermatitis-AD) and neoplastic (melanoma and non-melanoma-skin-cancer including squamous cell and basal cell carcinoma) diseases. In this scoping review article, the evidence recovered indicates that this topic has attracted attention, but it is still a matter of opinion. A protocol for this review was registered in PROSPERO with the registration number "CRD42023420245". According to the different skin disorders and to the specific cellular mechanisms considered (cancer stem cells, extracellular vesicles, inflammation), miRNAs may play a pro- or anti-inflammatory, as well as a tumor suppressive, or supporting, role, indicating a complex regulation of their function. It is evident that the mode of action of miRNAs is more than a switch on-off, and all the observed effects of their dysregulated expression must be checked in a detailed analysis of the targeted proteins. The involvement of miRNAs has been studied mainly for squamous cell carcinoma and melanoma, and much less in psoriasis and AD; different mechanisms have been considered, such as miRNAs included in extracellular vesicles derived both from MSCs or tumor cells, miRNAs involved in cancer stem cells formation, up to miRNAs as candidates to be new therapeutic tools.
Topics: Humans; MicroRNAs; Mesenchymal Stem Cells; Cell Differentiation; Skin Diseases; Neoplasms; Psoriasis
PubMed: 37239847
DOI: 10.3390/ijms24108502 -
Clinical Gastroenterology and... Dec 2020Liquid biopsies, or blood samples, can be analyzed to detect circulating tumor cells (CTCs), cell-free DNA (cfDNA), and extracellular vesicles, which might identify... (Review)
Review
BACKGROUND & AIMS
Liquid biopsies, or blood samples, can be analyzed to detect circulating tumor cells (CTCs), cell-free DNA (cfDNA), and extracellular vesicles, which might identify patients with hepatocellular carcinoma (HCC) or help determine their prognoses. We performed a systematic review of studies of analyses of liquid biopsies from patients with HCC and their comparisons with other biomarkers.
METHODS
We performed a systematic review of original studies published before December 1, 2019. We included studies that compared liquid biopsies alone and in combination with other biomarkers for the detection of HCC, performed multivariate analyses of the accuracy of liquid biopsy analysis in determining patient prognoses, or evaluated the utility of liquid biopsy analysis in monitoring treatment response.
RESULTS
Our final analysis included 112 studies: 67 on detection, 46 on determining prognosis, and 25 on treatment monitoring or selection. Ten studies evaluated assays that characterized cfDNA for detection of HCC in combination with measurement of α-fetoprotein (AFP)-these studies found that the combined measurement of cfDNA and AFP more accurately identified patients with HCC than measurement of AFP alone. Six studies evaluated assays for extracellular vesicles and 2 studies evaluated assays for CTC in detection of HCC, with and without other biomarkers-most of these studies found that detection of CTCs or extracellular vesicles with AFP more accurately identified patients with HCC than measurement of AFP alone. Detection of CTCs before surgery was associated with HCC recurrence after resection in 13 of 14 studies; cfDNA and extracellular vesicles have been studied less frequently as prognostic factors. Changes in CTC numbers before vs after treatment more accurately identify patients with HCC recurrence than pretreatment counts alone, and measurements of cfDNA can identify patients with disease recurrence or progression before changes can be detected by imaging. We found little evidence that analyses of liquid biopsies can aid in the selection of treatment for HCC. Quality assessment showed risk of bias in studies of HCC detection and determination of prognosis.
CONCLUSIONS
In a systematic review of 112 studies of the accuracy of liquid biopsy analysis, we found that assays for CTCs and cfDNA might aid in determining patient prognoses and monitoring HCC, and assays for cfDNA might aid in HCC detection, but there is a risk of bias in these studies. Studies must be standardized before we can assess the clinical utility of liquid biopsy analysis in the detection and management of patients with HCC.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Liquid Biopsy; Liver Neoplasms; Neoplasm Recurrence, Local; Prognosis; alpha-Fetoproteins
PubMed: 32289533
DOI: 10.1016/j.cgh.2020.04.019 -
Molecular Psychiatry Apr 2019Although synaptic loss is thought to be core to the pathophysiology of schizophrenia, the nature, consistency and magnitude of synaptic protein and mRNA changes has not... (Meta-Analysis)
Meta-Analysis
Although synaptic loss is thought to be core to the pathophysiology of schizophrenia, the nature, consistency and magnitude of synaptic protein and mRNA changes has not been systematically appraised. Our objective was thus to systematically review and meta-analyse findings. The entire PubMed database was searched for studies from inception date to the 1st of July 2017. We selected case-control postmortem studies in schizophrenia quantifying synaptic protein or mRNA levels in brain tissue. The difference in protein and mRNA levels between cases and controls was extracted and meta-analysis conducted. Among the results, we found a significant reduction in synaptophysin in schizophrenia in the hippocampus (effect size: -0.65, p < 0.01), frontal (effect size: -0.36, p = 0.04), and cingulate cortices (effect size: -0.54, p = 0.02), but no significant changes for synaptophysin in occipital and temporal cortices, and no changes for SNAP-25, PSD-95, VAMP, and syntaxin in frontal cortex. There were insufficient studies for meta-analysis of complexins, synapsins, rab3A and synaptotagmin and mRNA measures. Findings are summarised for these, which generally show reductions in SNAP-25, PSD-95, synapsin and rab3A protein levels in the hippocampus but inconsistency in other regions. Our findings of moderate-large reductions in synaptophysin in hippocampus and frontal cortical regions, and a tendency for reductions in other pre- and postsynaptic proteins in the hippocampus are consistent with models that implicate synaptic loss in schizophrenia. However, they also identify potential differences between regions and proteins, suggesting synaptic loss is not uniform in nature or extent.
Topics: Adult; Brain; Case-Control Studies; Disks Large Homolog 4 Protein; Female; Gyrus Cinguli; Hippocampus; Humans; Male; Middle Aged; RNA, Messenger; Schizophrenia; Synapses; Synapsins; Synaptic Vesicles; Synaptophysin; Synaptosomal-Associated Protein 25; Temporal Lobe; rab3A GTP-Binding Protein
PubMed: 29511299
DOI: 10.1038/s41380-018-0041-5 -
3 Biotech Mar 2022has emerged as one of major nosocomial pathogen and global emergence of multidrug-resistant strains has become a challenge for developing effective treatment options.... (Review)
Review
has emerged as one of major nosocomial pathogen and global emergence of multidrug-resistant strains has become a challenge for developing effective treatment options. has developed resistance to almost all the antibiotics viz beta-lactams, carbapenems, tigecycline and now colistin, a last resort of antibiotics. The world is on the cusp of post antibiotic era and the evolution of multi-, extreme- and pan-drug-resistant strains is its obvious harbinger. Various combinations of antibiotics have been investigated but no successful treatment option is available. All these failed efforts have led researchers to develop and implement prophylactic vaccination for the prevention of infections caused by this pathogen. In this review, the advantages and disadvantages of active and passive immunization, the types of sub-unit and multi-component vaccine candidates investigated against viz whole cell organism, outer membrane vesicles, outer membrane complexes, conjugate vaccines and sub-unit vaccines have been discussed. In addition, the benefits of Reverse vaccinology are emphasized here in which the potential vaccine candidates are predicted using bioinformatic online tools prior to in vivo validations.
PubMed: 35261870
DOI: 10.1007/s13205-022-03148-9 -
Thrombosis Research Mar 2018Despite high rates of venous thromboembolism (VTE) among patients with hematologic malignancies, few tools exist to assist providers in identifying those patients at... (Review)
Review
INTRODUCTION
Despite high rates of venous thromboembolism (VTE) among patients with hematologic malignancies, few tools exist to assist providers in identifying those patients at highest risk for this potentially fatal complication. Laboratory biomarkers, such as d-dimer, have demonstrated utility in some clinical settings to distinguish patients at increased risk.
MATERIALS AND METHODS
We performed a systematic review of the literature utilizing search terms including "biomarker", "venous thromboembolism", "hematologic malignancy", "lymphoma", "myeloma" and "leukemia" in the Medline database. A total of 25 studies investigating laboratory biomarkers of increased thrombotic risk in the setting of hematologic malignancy were identified and included in this review.
RESULTS AND CONCLUSIONS
The most studied biomarkers, d-dimer and fibrinogen, demonstrated some degree of efficacy in identifying high-risk patients at levels >4.0 mg/L or <1.0 g/L respectively. Additional markers which demonstrated promise included thrombin generation, mean platelet volume, soluble VEGF, soluble P-selectin and extracellular vesicles. Other biomarkers reviewed, which did not consistently demonstrate significant associations with VTE included prothrombin fragments F1 + 2, factor VIII, protein C, protein S, von Willebrand antigen and activity, antithrombin, thrombin antithrombin complex, antiphospholopid antibody, plasminogen activator inhibitor, tissue factor pathway inhibitor and several variants associated with known hypercoagulable states (factor V Leiden, prothrombin gene variant, methylenetetrahydrofolate reductase variant). Data to support any of the biomarkers discussed here in routine clinical decision-making are currently lacking, but additional investigation in clinical studies, ideally in combination with clinical factors known to be associated with increased thrombotic risk, is warranted.
Topics: Biomarkers; Female; Hematologic Neoplasms; Humans; Male; Risk Factors; Venous Thromboembolism
PubMed: 29407626
DOI: 10.1016/j.thromres.2018.01.037