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Heart Failure Reviews Jan 2024Iron overload increases the production of harmful reactive oxygen species in the Fenton reaction, which causes oxidative stress in the body and lipid peroxidation in the... (Review)
Review
Iron overload increases the production of harmful reactive oxygen species in the Fenton reaction, which causes oxidative stress in the body and lipid peroxidation in the cell membrane, and eventually leads to ferroptosis. Diabetes is associated with increased intracellular oxidative stress, inflammation, autophagy, microRNA alterations, and advanced glycation end products (AGEs), which cause cardiac remodeling and cardiac diastolic contractile dysfunction, leading to the development of diabetic cardiomyopathy (DCM). While these factors are also closely associated with ferroptosis, more and more studies have shown that iron-mediated ferroptosis is an important causative factor in DCM. In order to gain fresh insights into the functions of ferroptosis in DCM, this review methodically summarizes the traits and mechanisms connected with ferroptosis and DCM.
Topics: Humans; Diabetic Cardiomyopathies; Ferroptosis; MicroRNAs; Autophagy; Diastole; Reactive Oxygen Species; Diabetes Mellitus
PubMed: 37555989
DOI: 10.1007/s10741-023-10336-z -
Journal of Stroke and Cerebrovascular... Nov 2023Stroke diagnosis is dependent on lengthy clinical and neuroimaging assessments, while rapid treatment initiation improves clinical outcome. Currently, more sensitive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stroke diagnosis is dependent on lengthy clinical and neuroimaging assessments, while rapid treatment initiation improves clinical outcome. Currently, more sensitive biomarker assays of both non-coding RNA- and protein biomarkers have improved their detectability, which could accelerate stroke diagnosis. This systematic review and meta-analysis compares non-coding RNA- with protein biomarkers for their potential to diagnose and differentiate acute stroke (subtypes) in (pre-)hospital settings.
METHODS
We performed a systematic review and meta-analysis of studies evaluating diagnostic performance of non-coding RNA- and protein biomarkers to differentiate acute ischemic and hemorrhagic stroke, stroke mimics, and (healthy) controls. Quality appraisal of individual studies was assessed using the QUADAS-2 tool while the meta-analysis was performed with the sROC approach and by assessing pooled sensitivity and specificity, diagnostic odds ratios, positive- and negative likelihood ratios, and the Youden Index.
SUMMARY OF REVIEW
112 studies were included in the systematic review and 42 studies in the meta-analysis containing 11627 patients with ischemic strokes, 2110 patients with hemorrhagic strokes, 1393 patients with a stroke mimic, and 5548 healthy controls. Proteins (IL-6 and S100 calcium-binding protein B (S100B)) and microRNAs (miR-30a) have similar performance in ischemic stroke diagnosis. To differentiate between ischemic- or hemorrhagic strokes, glial fibrillary acidic protein (GFAP) levels and autoantibodies to the NR2 peptide (NR2aAb, a cleavage product of NMDA neuroreceptors) were best performing whereas no investigated protein or non-coding RNA biomarkers differentiated stroke from stroke mimics with high diagnostic potential.
CONCLUSIONS
Despite sampling time differences, circulating microRNAs (< 24 h) and proteins (< 4,5 h) perform equally well in ischemic stroke diagnosis. GFAP differentiates stroke subtypes, while a biomarker panel of GFAP and UCH-L1 improved the sensitivity and specificity of UCH-L1 alone to differentiate stroke.
Topics: Humans; Hemorrhagic Stroke; Stroke; Biomarkers; Ischemic Stroke; Glial Fibrillary Acidic Protein; MicroRNAs; RNA, Untranslated
PubMed: 37778160
DOI: 10.1016/j.jstrokecerebrovasdis.2023.107388 -
Journal of Controlled Release :... Sep 2022Gliomas are the deadliest of all primary brain tumors, and they constitute a serious global health problem. MicroRNAs (miRNAs) are gene expression regulators associated... (Review)
Review
Gliomas are the deadliest of all primary brain tumors, and they constitute a serious global health problem. MicroRNAs (miRNAs) are gene expression regulators associated with glioma pathogenesis. Thus, miRNAs represent potential therapeutic agents for treating gliomas. However, miRNAs have not been established as part of the regular clinical armamentarium. This systemic review evaluates current molecular and pre-clinical studies with the aim of defining the most appealing supramolecular platform for administering therapeutic miRNA to patients with gliomas. An integrated analysis suggested that cationic lipid nanoparticles, functionalized with octa-arginine peptides, represent a potentially specific, practical, non-invasive intervention for treating gliomas. This supramolecular platform allows loading both hydrophilic (miRNA) and hydrophobic (anti-tumor drugs, like temozolomide) molecules. This systemic review is the first to describe miRNA delivery systems targeted to gliomas that integrate several types of molecules as active ingredients. Further experimental validation is warranted to confirm the practical value of miRNA delivery systems.
Topics: Arginine; Brain Neoplasms; Glioma; Humans; Liposomes; MicroRNAs; Nanoparticles; Peptides; Temozolomide
PubMed: 35905783
DOI: 10.1016/j.jconrel.2022.07.027 -
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 -
Cells Jun 2023Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating... (Review)
Review
Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating evidence has shown that small single-stranded non-coding microRNAs (miRNAs) act as powerful endogenous regulators of TEC function and blood vessel formation. This systematic review provides an up-to-date overview of these endothelial miRNAs. Their expression is mainly regulated by hypoxia, pro-angiogenic factors, gap junctions and extracellular vesicles, as well as long non-coding RNAs and circular RNAs. In preclinical studies, they have been shown to modulate diverse fundamental angiogenesis-related signaling pathways and proteins, including the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway; the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; the phosphoinositide 3-kinase (PI3K)/AKT pathway; and the transforming growth factor (TGF)-β/TGF-β receptor (TGFBR) pathway, as well as krüppel-like factors (KLFs), suppressor of cytokine signaling (SOCS) and metalloproteinases (MMPs). Accordingly, endothelial miRNAs represent promising targets for future anti-angiogenic cancer therapy. To achieve this, it will be necessary to further unravel the regulatory and functional networks of endothelial miRNAs and to develop safe and efficient TEC-specific miRNA delivery technologies.
Topics: Humans; MicroRNAs; Endothelial Cells; Vascular Endothelial Growth Factor A; Phosphatidylinositol 3-Kinases; Neoplasms; Mitogen-Activated Protein Kinase Kinases; Receptors, Vascular Endothelial Growth Factor; Tumor Microenvironment
PubMed: 37443725
DOI: 10.3390/cells12131692 -
Free Radical Biology & Medicine Aug 2021Although myocardial ischemia-reperfusion injury (I/R) and its pathological consequences are the leading cause of morbidity and mortality worldwide, cardioprotective... (Review)
Review
Systematic review and network analysis of microRNAs involved in cardioprotection against myocardial ischemia/reperfusion injury and infarction: Involvement of redox signalling.
Although myocardial ischemia-reperfusion injury (I/R) and its pathological consequences are the leading cause of morbidity and mortality worldwide, cardioprotective therapeutics are still not on the market. Oxidative stress, a major contributing factor to myocardial I/R, changes transcription of coding and non-coding RNAs, alters post-transcriptional modulations, and regulate protein function. MicroRNA (miRNA) expression can be altered by oxidative stress and microRNAs may also regulate cytoprotective mechanisms and exert cardioprotection againts I/R. Transcriptomic analysis of I/R and oxidative stress-induced alterations followed by microRNA-mRNA target interaction network analysis may reveal microRNAs and their mRNA targets that may play a role in cardioprotection and serve as microRNA therapeutics or novel molecular targets for further drug development. Here we provide a summary of a systematic literature review and in silico molecular network analysis to reveal important cardioprotective microRNAs and their molecular targets that may provide cardioprotection via regulation of redox signalling.
Topics: Humans; Infarction; MicroRNAs; Myocardial Reperfusion Injury; Oxidation-Reduction; Signal Transduction
PubMed: 33965565
DOI: 10.1016/j.freeradbiomed.2021.04.034 -
Clinical and Experimental Medicine Nov 2023Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases globally, leading to chronic disability and poor prognosis. One of the approaches for... (Meta-Analysis)
Meta-Analysis
Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases globally, leading to chronic disability and poor prognosis. One of the approaches for optimizing OA treatment is to find early effective diagnostic biomarkers. The contribution of microRNAs (miRNAs) in OA progression is now being increasingly recognized. This review provides a comprehensive summary on studies reporting the expression profiling of miRNAs in OA and associated signaling pathways. We performed a systematic search of the Embase, Web of Science, PubMed, and Cochrane library databases. This systematic review is reported according to the PRISMA checklist. Studies which identified miRNAs with aberrant expression compared to controls during OA progression were included, and a meta-analysis was performed. Results from the random effects model were provided as log10 odds ratios (logORs) and 95% confidence intervals. Sensitivity analysis was conducted to confirm the accuracy of the results. Subgroup analysis was conducted based on tissue source. The target genes of miRNAs identified in this study were extracted from the MiRWalk database, and these target genes were enriched in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. A total of 191 studies reporting 162 miRNAs were included in our meta-analysis. Among them, 36 miRNAs distributed across 96 studies were expressed in the same direction in at least two studies (13 up-regulated and 23 down-regulated). Subgroup analysis of tissue source revealed that the highest number of studies was conducted using articular cartilage, where the most up-regulated miRNAs were miR-146a-5p (logOR 7.355; P < 0.001) and miR-34a-5p (logOR 6.955; P < 0.001), and the most down-regulated miRNAs were miR-127-5p (logOR 6.586; P < 0.001) and miR-140-5p (logOR 6.373; P < 0.001). Enrichment analysis of 752 downstream target genes of all identified miRNAs was performed, and the regulatory relationships among them were displayed. Mesenchymal stem cells and transforming growth factor-β were found to be the most important downstream effectors regulated by miRNA in OA. This study highlighted the importance of miRNA signaling in OA progression and identified a number of prominent miRNAs including miR-146a-5p, miR-34a-5p, miR-127-5p, and miR-140-5p which might be considered as potential biomarkers for OA.
Topics: Humans; MicroRNAs; Osteoarthritis; Biomarkers
PubMed: 37027064
DOI: 10.1007/s10238-023-01063-8 -
Expert Review of Molecular Diagnostics 2023Early and non-invasive detection of hepatocellular carcinoma (HCC), which is usually asymptomatic, can improve overall survival outcomes. The objective of this... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Early and non-invasive detection of hepatocellular carcinoma (HCC), which is usually asymptomatic, can improve overall survival outcomes. The objective of this systematic review and meta-analysis was to evaluate the diagnostic accuracy of serum-derived exosomes for diagnosing HCC.
METHODS
PubMed, Web of Science, and Scopus databases were searched for relevant studies up to April 2023. The quality of included studies was assessed using the QUADAS-2 checklist, and data were extracted. Statistical analysis was performed on 18 studies from 3,993 records, and a diagnostic meta-analysis was conducted. Biomarkers were categorized into four groups based on their type (exosomal miRNAs, exosomal RNAs, alpha-fetoprotein (AFP), and exosomal RNAs+AFP panel), and a meta-analysis was conducted for each category separately.
RESULTS
The highest pooled sensitivity was 0.86 for exosomal miRNAs, and exosomal RNAs+AFP had the highest pooled specificity; (0.89). Furthermore, exosomal RNAs+AFP had the highest pooled positive likelihood ratio; (7.55), the highest pooled diagnostic odds ratio (35.96) and the highest pooled area under the curve (0.93). Exosomal miRNAs had the lowest pooled negative likelihood ratio; (0.17).
CONCLUSIONS
The diagnostic accuracy of exosomal biomarkers is superior to that of AFP, and combining the two in a panel yields the better results.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Exosomes; Biomarkers; MicroRNAs; Biomarkers, Tumor
PubMed: 37715364
DOI: 10.1080/14737159.2023.2260306 -
EBioMedicine Jul 2023Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently...
BACKGROUND
Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently validated, and some results are contradictory. We provided a comprehensive evaluation of various types of cfRNA biomarkers and a full mining of the biomarker potential of new features of cfRNA.
METHODS
We first systematically reviewed reported cfRNA biomarkers and calculated dysregulated post-transcriptional events and cfRNA fragments. In 3 independent multicentre cohorts, we further selected 6 cfRNAs using RT-qPCR, built a panel called HCCMDP with AFP using machine learning, and internally and externally validated HCCMDP's performance.
FINDINGS
We identified 23 cfRNA biomarker candidates from a systematic review and analysis of 5 cfRNA-seq datasets. Notably, we defined the cfRNA domain to describe cfRNA fragments systematically. In the verification cohort (n = 183), cfRNA fragments were more likely to be verified, while circRNA and chimeric RNA candidates were neither abundant nor stable as qPCR-based biomarkers. In the algorithm development cohort (n = 287), we build and test the panel HCCMDP with 6 cfRNA markers and AFP. In the independent validation cohort (n = 171), HCCMDP can distinguish HCC patients from control groups (all: AUC = 0.925; CHB: AUC = 0.909; LC: AUC = 0.916), and performs well in distinguishing early-stage HCC patients (all: AUC = 0.936; CHB: AUC = 0.917; LC: AUC = 0.928).
INTERPRETATION
This study comprehensively evaluated full-spectrum cfRNA biomarker types for HCC detection, highlighted the cfRNA fragment as a promising biomarker type in HCC detection, and provided a panel HCCMDP.
FUNDING
National Natural Science Foundation of China, and The National Key Basic Research Program (973 program).
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Cell-Free Nucleic Acids; Biomarkers, Tumor; ROC Curve; MicroRNAs
PubMed: 37315449
DOI: 10.1016/j.ebiom.2023.104645 -
CNS Neuroscience & Therapeutics Aug 2023Rapid diagnosis of acute ischemic stroke (AIS) patients is still challenging, and reliable biomarkers are needed. Noncoding RNAs are important for many physiological... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rapid diagnosis of acute ischemic stroke (AIS) patients is still challenging, and reliable biomarkers are needed. Noncoding RNAs are important for many physiological activities, among which circular RNAs (circRNAs) have been proven to be more tissue-specific and conservative. Many recent studies found the potential of circRNAs as biomarkers for many diseases, including cardiovascular diseases, cancers, and ischemic stroke. This systemic review and meta-analysis aimed to identify circRNAs as potential biomarkers for AIS.
METHODS
This study has been prospectively registered in PROSPERO (Registration No. 11 CRD42021288033). Published literature comparing circRNA expression profiles between AIS and non-AIS in human and animal models were retrieved from the articles published by January 2023 in major databases. We descriptively summarized the included studies, conducted meta-analysis under a random effects model, and did bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.
RESULTS
Totally 23 studies were included, reporting 18 distinctive upregulated and 20 distinctive downregulated circRNAs. Diagnostic meta-analysis indicated discriminative ability of the circRNAs. Furthermore, circRNA HECTD1, circRNA DLGAP4, circRNA CDC14A, circRNA SCMH1, and circRNA TLK1 were reported with the same regulation trend in more than one study (animal studies included). GO and KEGG enrichment analyses indicated that the target genes of these five circRNAs were enriched in regulating cell proliferation, apoptosis, and oxidative stress.
CONCLUSIONS
This study demonstrates that circRNAs (circRNA HECTD1, circRNA DLGAP4, circRNA CDC14A, circRNA SCMH1, and circRNA TLK1) generally are promising as potential biomarkers for AIS. However, due to the limited number of studies, diagnostic value of individual circRNA could not be validated. More in vitro and in vivo functional studies are needed.
Topics: Animals; Humans; RNA, Circular; Ischemic Stroke; Stroke; Biomarkers; MicroRNAs; RNA; Gene Expression Profiling; Protein Serine-Threonine Kinases
PubMed: 37186176
DOI: 10.1111/cns.14220