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Scientific Reports Sep 2023Current clinical tests for Parkinson's disease (PD) provide insufficient diagnostic accuracy leading to an urgent need for improved diagnostic biomarkers. As microRNAs... (Meta-Analysis)
Meta-Analysis
Current clinical tests for Parkinson's disease (PD) provide insufficient diagnostic accuracy leading to an urgent need for improved diagnostic biomarkers. As microRNAs (miRNAs) are promising biomarkers of various diseases, including PD, this systematic review and meta-analysis aimed to assess the diagnostic accuracy of biofluid miRNAs in PD. All studies reporting data on miRNAs expression in PD patients compared to controls were included. Gene targets and significant pathways associated with miRNAs expressed in more than 3 biofluid studies with the same direction of change were analyzed using target prediction and enrichment analysis. A bivariate model was used to calculate sensitivity, specificity, likelihood ratios, and diagnostic odds ratio. While miR-24-3p and miR-214-3p were the most reported miRNA (7 each), miR-331-5p was found to be consistently up regulated in 4 different biofluids. Importantly, miR-19b-3p, miR-24-3p, miR-146a-5p, and miR-221-3p were reported in multiple studies without conflicting directions of change in serum and bioinformatic analysis found the targets of these miRNAs to be associated with pathways important in PD pathology. Of the 102 studies from the systematic review, 15 studies reported sensitivity and specificity data on combinations of miRNAs and were pooled for meta-analysis. Studies (17) reporting sensitivity and specificity data on single microRNA were pooled in a separate meta-analysis. Meta-analysis of the combinations of miRNAs (15 studies) showed that biofluid miRNAs can discriminate between PD patients and controls with good diagnostic accuracy (sensitivity = 0.82, 95% CI 0.76-0.87; specificity = 0.80, 95% CI 0.74-0.84; AUC = 0.87, 95% CI 0.83-0.89). However, we found multiple studies included more males with PD than any other group therefore possibly introducing a sex-related selection bias. Overall, our study captures key miRNAs which may represent a point of focus for future studies and the development of diagnostic panels whilst also highlighting the importance of appropriate study design to develop representative biomarker panels for the diagnosis of PD.
Topics: Male; Humans; MicroRNAs; Parkinson Disease; Biomarkers; Sensitivity and Specificity
PubMed: 37770507
DOI: 10.1038/s41598-023-43096-9 -
Biomedicines Sep 2023Psychotic disorders are a heterogenous class of mental illness, with an intricate pathophysiology, involving genetics and environmental factors, and their interaction.... (Review)
Review
Psychotic disorders are a heterogenous class of mental illness, with an intricate pathophysiology, involving genetics and environmental factors, and their interaction. The identification of accessible biomarkers in bodily systems such as blood may lead to more accurate diagnosis, and more effective treatments targeting dysfunctional pathways, and could assist in monitoring the disease evolution. This systematic review aims to highlight the dysregulated microRNAs (miRNAs) in the peripheral blood of patients with psychotic disorders. Using the PRISMA protocol, PubMed and Science Direct databases were investigated and 22 articles were included. Fifty-five different miRNAs were found differentially expressed in the blood of psychotic patients compared to controls. Seventeen miRNAs (miR-34a, miR-181b, miR-432, miR-30e, miR-21, miR-137, miR-134, miR-7, miR-92a, miR-1273d, miR-1303, miR-3064-5p, miR-3131, miR-3687, miR-4428, miR-4725-3p, and miR-5096) were dysregulated with the same trend (up- or down-regulation) in at least two studies. Of note, miR-34a and miR-181b were up-regulated in the blood of psychotic patients in seven and six studies, respectively. Moreover, the level of miR-181b in plasma was found to be positively correlated with the amelioration of negative symptoms. The panel of miRNAs identified in this review could be validated in future studies in large and well-characterized cohorts of psychotic patients.
PubMed: 37760977
DOI: 10.3390/biomedicines11092536 -
Cureus Aug 2023Pancreatic cancer (PC) is one of the most common cancers and has a high mortality rate due to high invasiveness and rapid progression. Microribonucleic acid (microRNA)... (Review)
Review
Pancreatic cancer (PC) is one of the most common cancers and has a high mortality rate due to high invasiveness and rapid progression. Microribonucleic acid (microRNA) plays an essential role in diagnosing PC in the early stages, which improves the five-year survival rate. This systematic review aims to highlight the different subtypes of serum and plasma microRNAs and panel-based assays of microRNAs and how they play a crucial role in the diagnosis and prognosis of PC as a high-sensitive and specific novel biomarker. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines, an in-depth search was performed by using regular keywords and major Medical Subject Heading (MeSH) keywords in PubMed (MEDLINE), PubMed Central, Google Scholar, Science Direct, and Cochrane Library for articles related to this topic and published between 2013 and 2023, up to April 18, 2023. Further eligibility criteria and quality assessment tools were employed to assess the risk of bias, and 13 articles were finalized to be used in this review. The chosen articles included five cross-sectional studies, six systematic reviews and meta-analyses, and two literature reviews. This review provides strong evidence of the usage of microRNA for early diagnosis. It can also be used to exclude differential diagnoses of other diseases, and its prognostic value for determining metastasis and therapeutic efficacy in PC patients. Also, combining microRNA panels with carbohydrate antigen 19.9 (CA19-9) improves the sensitivity and specificity of microRNA as a biomarker.
PubMed: 37746488
DOI: 10.7759/cureus.43931 -
Diabetes & Metabolic Syndrome Oct 2023Atherosclerosis in carotid arteries can remain clinically undetected in its early development until an acute cerebrovascular event such as stroke emerges. Recently,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Atherosclerosis in carotid arteries can remain clinically undetected in its early development until an acute cerebrovascular event such as stroke emerges. Recently, microRNAs (miRNAs) circulating in blood have emerged as potential diagnostic biomarkers, but their performance in detecting subclinical carotid atherosclerosis has yet to be systematically researched.
AIM
To investigate the diagnostic performance of circulating miRNAs in detecting subclinical carotid atherosclerosis.
METHODS
We systematically searched five electronic databases from inception to July 23, 2022. Subclinical carotid atherosclerosis was defined using carotid intima-media thickness (CIMT). Diagnostic accuracy parameters and correlation coefficients were pooled. A gene network visualisation and enrichment bioinformatics analysis were additionally conducted to search for potential target genes and pathway regulations of the miRNAs.
RESULTS
Fifteen studies (15 unique miRNAs) comprising 2542 subjects were identified. Circulating miRNAs had a pooled sensitivity of 85% (95% CI 80%-89%), specificity of 84% (95% CI 78%-88%), positive likelihood ratio of 5.19 (95% CI 3.97-6.80), negative likelihood ratio of 0.18 (95% CI 0.13-0.23), diagnostic odds ratio of 29.48 (95% CI 21.15-41.11), and area under the summary receiver operating characteristic curve of 0.91 (95% CI 0.88-0.93), with a strong correlation to CIMT (pooled coefficient 0.701; 95% CI 0.664-0.731). Bioinformatics analysis revealed a major role of the miRNAs, as shown by their relation with CCND1, KCTD15, SPARC, WWTR1, VEGFA genes, and multiple pathways involved in the pathogenesis of carotid atherosclerosis.
CONCLUSION
Circulating miRNAs had excellent accuracy in detecting subclinical carotid atherosclerosis, suggesting their utilisation as novel diagnostic tools.
Topics: Humans; MicroRNAs; Carotid Intima-Media Thickness; Carotid Artery Diseases; Atherosclerosis; Biomarkers
PubMed: 37742360
DOI: 10.1016/j.dsx.2023.102860 -
Non-coding RNA Sep 2023Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have... (Review)
Review
Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have been identified as pivotal players in the onset and advancement of HNSCCs, operating as either oncogenes or tumor suppressors. Distinctive miR patterns identified in tumor samples, as well as in serum, plasma, or saliva, from patients have significant clinical potential for use in the diagnosis and prognosis of HNSCCs and as potential therapeutic targets. The aim of this study was to identify previous systematic reviews with meta-analysis data and clinical trials that showed the most promising miRs in HNSCCs, enclosing them into a biomolecular signature to test the prognostic value on a cohort of HNSCC patients according to The Cancer Genome Atlas (TCGA). Three electronic databases (PubMed, Scopus, and Science Direct) and one registry (the Cochrane Library) were investigated, and a combination of keywords such as "signature microRNA OR miR" AND "HNSCC OR LSCC OR OSCC OR oral cancer" were searched. In total, 15 systematic literature reviews and 76 prognostic clinical reports were identified for the study design and inclusion process. All survival index data were extracted, and the three miRs (miR-21, miR-155, and miR-375) most investigated and presenting the largest number of patients included in the studies were selected in a molecular biosignature. The difference between high and low tissue expression levels of miR-21, miR-155, and miR-375 for OS had an HR = 1.28, with 95% CI: [0.95, 1.72]. In conclusion, the current evidence suggests that miRNAs have potential prognostic value to serve as screening tools for clinical practice in HNSCC follow-up and treatment. Further large-scale cohort studies focusing on these miRNAs are recommended to verify the clinical utility of these markers individually and/or in combination.
PubMed: 37736900
DOI: 10.3390/ncrna9050054 -
Non-coding RNA Sep 2023Obesity is an important risk factor for cardiovascular disease and type 2 diabetes mellitus. Even a modest weight loss of 5-15% improves metabolic health, but... (Review)
Review
Obesity is an important risk factor for cardiovascular disease and type 2 diabetes mellitus. Even a modest weight loss of 5-15% improves metabolic health, but circulating markers to indicate weight loss efficiency are lacking. MicroRNAs, small non-coding post-transcriptional regulators of gene expression, are secreted from tissues into the circulation and may be potential biomarkers for metabolic health. However, it is not known which specific microRNA species are reproducibly changed in levels by weight loss. In this study, we performed a systematic review and meta-analysis to investigate the microRNAs associated with weight loss by comparing baseline to follow-up levels following intervention-driven weight loss. This systematic review was performed according to the PRISMA guidelines with searches in PubMed and SCOPUS. The primary search resulted in a total of 697 articles, which were screened according to the prior established inclusion and exclusion criteria. Following the screening of articles, the review was based on the inclusion of 27 full-text articles, which were evaluated for quality and the risk of bias. We performed systematic data extraction, whereafter the relative values for miRNAs were calculated. A meta-analysis was performed for the miRNA species investigated in three or more studies: miR-26a, miR-126, and miR-223 were overall significantly increased following weight loss, while miR-142 was significantly decreased after weight loss. miR-221, miR-140, miR-122, and miR-146 were not significantly changed by intervention-driven weight loss. These results indicate that few miRNAs are significantly changed during weight loss.
PubMed: 37736899
DOI: 10.3390/ncrna9050053 -
Stem Cells Translational Medicine Dec 2023The development of extracellular vesicles (EVs) therapies has revolutionized personalized medicine, opening up new possibilities for treatment. EVs have emerged as a...
The development of extracellular vesicles (EVs) therapies has revolutionized personalized medicine, opening up new possibilities for treatment. EVs have emerged as a promising therapeutic tool within this field due to their crucial role in intercellular communication across various cell types and organisms. This systematic review aims to evaluate the therapeutic potential of oral mesenchymal stem cell (MSC)-derived EVs for bone regeneration, specifically focusing on findings from preclinical models. Sixteen articles meeting the inclusion criteria were selected following document analysis. The biological effects of oral MSC-derived EVs predominantly involve the upregulation of proteins associated with angiogenesis, and inflammation resolution, alongside the downregulation of proinflammatory cytokines. Moreover, these therapeutic agents have been found to contain a significant quantity of different molecules (proteins, lipids, DNA, microRNAs, etc) further contributing to their modulatory potential. The findings from this systematic review underscore that oral MSC-derived EVs, irrespective of their specific population, have the ability to enhance the osteogenic repair response in maxillary bone or periodontal defects. In summary, this systematic review highlights the promising potential of oral MSC-derived EVs for bone regeneration based on evidence from preclinical models. The comprehensive assessment of their biological effects and the presence of microRNAs underscores their therapeutic significance. These findings support the utilization of oral MSC-derived EVs in enhancing the osteogenic repair response in various maxillary bone or periodontal defects, providing insights into the mechanisms involved and potential therapeutic applications in the field of personalized medicine.
Topics: Mesenchymal Stem Cells; Extracellular Vesicles; MicroRNAs; Bone Regeneration; Osteogenesis
PubMed: 37715961
DOI: 10.1093/stcltm/szad059 -
Cellular and Molecular Neurobiology Nov 2023Liquid biopsy research on Low-Grade gliomas (LGG) has remained less conspicuous than that on other malignant brain tumors. Reliable serum markers would be precious for... (Review)
Review
Liquid biopsy research on Low-Grade gliomas (LGG) has remained less conspicuous than that on other malignant brain tumors. Reliable serum markers would be precious for diagnosis, follow- up and treatment. We propose a clinical utility score (CUS) for biomarkers in LGG that mirrors their clinical usefulness. We conducted a PRISMA review. We examined each biomarker classifying them by CUS and Level of Evidence (LOE). We identified four classes of biomarkers: (1). Circulating protein-(a) vitronectin discriminates LGG from HGG (Sn:98%, Sp:91%, CUS: 3, LOE: III), (b) CTLA-4 discriminates LGG from HGG, (cutoff: 220.43 pg/ml, Sn: 82%, Sp: 78%, CUS:3, LOE:III), (c) pre-operative TGF b1 predict astrocytoma (cutoff: 2.52 ng/ml, Sn: 94.9%, Sp: 100%, CUS:3, LOE:VI). (2). micro-RNA (miR)-(a) miR-16 discriminates between WHO IV and WHO II and III groups (AUC = 0.98, CUS:3, LOE: III), (b) miR-454-3p is higher in HGG than in LGG (p = 0.013, CUS:3, LOE: III), (c) miR-210 expression is related to WHO grades (Sn 83.2%, Sp 94.3%, CUS: 3, LOE: III). (3). Circulating DNA-(a) IDH1R132H mutation detected in plasma by combined COLD and digital PCR (Sn: 60%, Sp: 100%, CUS: 3, LOE: III). 4. Exosomes-(a) SDC1 serum levels could discriminate GBM from LGG (Sn: 71%, Sp: 91%, CUS: 2C, LOE: VI). Our investigation showed that miRs appear to have the highest clinical utility. The LOE of the studies assessed is generally low. A combined approach between different biomarkers and traditional diagnostics may be considered. We identified four main classes of biomarkers produced by LGG. We examined each biomarker, classifying them by clinical utility score (CUS) and level of evidence (LOE). Micro-RNA (miRs) appears to have the highest CUS and LOE.
Topics: Humans; Glioma; Brain Neoplasms; Biomarkers, Tumor; Liquid Biopsy; MicroRNAs; Neoplasm Grading
PubMed: 37704931
DOI: 10.1007/s10571-023-01406-9 -
Oncology Letters Oct 2023The prognosis of a gastric cancer (GC) diagnosis is poor due to the current lack of effective early diagnostic methods. Extracellular vesicle (EV) biomarkers have...
The prognosis of a gastric cancer (GC) diagnosis is poor due to the current lack of effective early diagnostic methods. Extracellular vesicle (EV) biomarkers have previously demonstrated strong diagnostic efficiency for certain types of cancer, including pancreatic and lung cancer. The present review aimed to summarize the diagnostic value of circulating EV biomarkers for early stage GC. The PubMed, Medline and Web of Science databases were searched from May 1983 to September 18, 2022. All studies that reported the diagnostic performance of EV biomarkers for GC were included for analysis. Overall, 27 studies were selected containing 2,831 patients with GC and 2,117 controls. A total of 58 EV RNAs were reported in 26 studies, including 39 microRNAs (miRNAs), 10 long non-coding RNAs (lncRNAs), five circular RNAs, three PIWI-interacting RNAs and one mRNA, in addition to one protein in the remaining study. Meta-analysis of the aforementioned studies demonstrated that the pooled sensitivity, specificity and AUC value of the total RNAs were 84, 67% and 0.822, respectively. The diagnostic values of miRNAs were consistent with the total RNA, as the pooled sensitivity, specificity and AUC value were 84, 67% and 0.808, respectively. The pooled sensitivity, specificity and AUC values of lncRNAs were 89, 69% and 0.872, respectively, markedly higher compared with that of miRNAs. A total of five studies reported the diagnostic performance of EV RNA panels for early stage GC and reported powerful diagnostic values with a pooled sensitivity, specificity and AUC value of 80, 77% and 0.879, respectively. Circulating EV RNAs could have the potential to be used in the future as effective, noninvasive biomarkers for early GC diagnosis. Further research in this field is necessary to translate these findings into clinical practice.
PubMed: 37664665
DOI: 10.3892/ol.2023.14009 -
Frontiers in Oncology 2023Research on hepatocellular carcinoma (HCC) has grown significantly, and researchers cannot access the vast amount of literature. This study aimed to explore the research... (Review)
Review
INTRODUCTION
Research on hepatocellular carcinoma (HCC) has grown significantly, and researchers cannot access the vast amount of literature. This study aimed to explore the research progress in studying HCC over the past 30 years using a machine learning-based bibliometric analysis and to suggest future research directions.
METHODS
Comprehensive research was conducted between 1991 and 2020 in the public version of the PubMed database using the MeSH term "hepatocellular carcinoma." The complete records of the collected results were downloaded in Extensible Markup Language format, and the metadata of each publication, such as the publication year, the type of research, the corresponding author's country, the title, the abstract, and the MeSH terms, were analyzed. We adopted a latent Dirichlet allocation topic modeling method on the Python platform to analyze the research topics of the scientific publications.
RESULTS
In the last 30 years, there has been significant and constant growth in the annual publications about HCC (annual percentage growth rate: 7.34%). Overall, 62,856 articles related to HCC from the past 30 years were searched and finally included in this study. Among the diagnosis-related terms, "Liver Cirrhosis" was the most studied. However, in the 2010s, "Biomarkers, Tumor" began to outpace "Liver Cirrhosis." Regarding the treatment-related MeSH terms, "Hepatectomy" was the most studied; however, recent studies related to "Antineoplastic Agents" showed a tendency to supersede hepatectomy. Regarding basic research, the study of "Cell Lines, Tumors,'' appeared after 2000 and has been the most studied among these terms.
CONCLUSION
This was the first machine learning-based bibliometric study to analyze more than 60,000 publications about HCC over the past 30 years. Despite significant efforts in analyzing the literature on basic research, its connection with the clinical field is still lacking. Therefore, more efforts are needed to convert and apply basic research results to clinical treatment. Additionally, it was found that microRNAs have potential as diagnostic and therapeutic targets for HCC.
PubMed: 37664017
DOI: 10.3389/fonc.2023.1227991