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Multifaceted and Diversified Roles of MicroRNAs in Health, Diseases and Death

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 6746

Special Issue Editors

Dr. Massimiliano Esposito

E-Mail Website
Guest Editor
Department of Medical, Surgical and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95121 Catania, Italy
Interests: forensic pathology; high biological risk autopsies (as COVID-19); molecular autopsy; histopathology; forensic genetics; forensic toxicology; criminalistics; forensic evidence; forensic biology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Cristoforo Pomara

E-Mail Website
Guest Editor
Department of Medical, Surgical and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95121 Catania, Italy
Interests: forensics; autopsy; forensic pathology; forensic toxicology; drugs of abuse; postmortem; technology and forensics; genomic application in pathology; anabolic androgenic steroids
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

MiRNA is a class of small (about 22 nt long) noncoding RNAs whose main function is in negative post-transcriptional and translational regulation of gene expression. Many of them show a differential expression in differentiation and disease and possess a heretofore unknown function. For example, lately, it was noted that MiRNAs are involved in the regulation of the circadian rhythm. In some patients with circadian rhythm disorders and in some neurodegenerative diseases, alterations of the brain MiRNAs, responsible for the sleep/wake cycle, were studied. It is thought that specific studies on these targets could also play a key role in the therapy of these neurodegenerative diseases.

MiRNA levels could also be used to identify pathophysiological conditions of disease and injury as well as the duration of agony or other premortem factors, which is why MiRNA has attracted increasing interest in crime scene investigation, too. Tissue-specific miRNAs can be used to determine the type of body fluid present in a crime scene stain, and they can also be used to assess wound vitality. Recent experimental studies have investigated the importance of MiRNAs in traumatic brain injury (TBI), as these biomarkers could be used for the identification of the anatomical region of brain damage and, consequently, the exact cause of death, also distinguishing mild from severe brain damage. Finally, even in cases of malpractice claims, such as in sepsis caused by hospital-acquired infections, MiRNAs are useful tools as potential sepsis biomarkers.

This Special Issue aims collect research articles and comprehensive reviews to offer an overview of the possible application of miRNA in pathophysiological conditions to develop strategies to treat or identify these diseases.

Dr. Massimiliano Esposito
Prof. Dr. Cristoforo Pomara
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • miRNA
  • brain injury
  • neurodegenerative diseases
  • PMI
  • sepsis
  • bloodstain
  • molecular autopsy
  • circadian rhythm

Published Papers (4 papers)

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Research

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11 pages, 1666 KiB  
Article
Evaluation of a Set of miRNAs in 26 Cases of Fatal Traumatic Brain Injuries
by Serena Bonin, Stefano D’Errico, Caterina Medeot, Carlo Moreschi, Solange Sorçaburu Ciglieri, Michela Peruch, Monica Concato, Eros Azzalini, Carlo Previderè and Paolo Fattorini
Int. J. Mol. Sci. 2023, 24(13), 10836; https://doi.org/10.3390/ijms241310836 - 29 Jun 2023
Viewed by 823
Abstract
In forensic medicine, identifying novel biomarkers for use as diagnostic tools to ascertain causes of death is challenging because of sample degradation. To that aim, a cohort (n = 26) of fatal traumatic brain injuries (TBIs) were tested for three candidate miRNAs [...] Read more.
In forensic medicine, identifying novel biomarkers for use as diagnostic tools to ascertain causes of death is challenging because of sample degradation. To that aim, a cohort (n = 26) of fatal traumatic brain injuries (TBIs) were tested for three candidate miRNAs (namely, miR-124-3p, miR-138-5p, and miR144-3p). For each case, three FFPE specimens (coup area (CA), contrecoup area (CCA), and the corpus callosum (CC)) were investigated, whereas the FFPE brain tissues of 45 subjects (deceased due to acute cardiovascular events) were used as controls. Relative quantification via the ∆∆Ct method returned significantly higher expression levels of the three candidate miRNAs (p < 0.01) in the TBI cases. No difference was detected in the expression levels of any miRNA investigated in the study among the CA, CCA, and CC. Furthermore, the analyzed miRNAs were unrelated to the TBI samples’ post-mortem intervals (PMIs). On the contrary, has-miR-124-3p ahashsa-miR-144-3p were significantly correlated (p < 0.01) with the agonal time in TBI deaths. Since the RNA was highly degraded in autoptic FFPE tissues, it was impossible to analyze the mRNA targets of the miRNAs investigated in the present study, highlighting the necessity of standardizing pre-analytical processes even for autopsy tissues. Full article
(This article belongs to the Special Issue Multifaceted and Diversified Roles of MicroRNAs in Health, Diseases and Death)
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11 pages, 1431 KiB  
Article
miRNA Expression Is Increased in Serum from Patients with Semantic Variant Primary Progressive Aphasia
by Maria Serpente, Laura Ghezzi, Chiara Fenoglio, Francesca R. Buccellato, Giorgio G. Fumagalli, Emanuela Rotondo, Marina Arcaro, Andrea Arighi and Daniela Galimberti
Int. J. Mol. Sci. 2022, 23(15), 8487; https://doi.org/10.3390/ijms23158487 - 30 Jul 2022
Viewed by 1818
Abstract
Primary progressive aphasia (PPA) damages the parts of the brain that control speech and language. There are three clinical PPA variants: nonfluent/agrammatic (nfvPPA), logopenic (lvPPA) and semantic (svPPA). The pathophysiology underlying PPA variants is not fully understood, including the role of micro (mi)RNAs [...] Read more.
Primary progressive aphasia (PPA) damages the parts of the brain that control speech and language. There are three clinical PPA variants: nonfluent/agrammatic (nfvPPA), logopenic (lvPPA) and semantic (svPPA). The pathophysiology underlying PPA variants is not fully understood, including the role of micro (mi)RNAs which were previously shown to play a role in several neurodegenerative diseases. Using a two-step analysis (array and validation through real-time PCR), we investigated the miRNA expression pattern in serum from 54 PPA patients and 18 controls. In the svPPA cohort, we observed a generalized upregulation of miRNAs with miR-106b-5p and miR-133a-3p reaching statistical significance (miR-106b-5p: 2.69 ± 0.89 mean ± SD vs. 1.18 ± 0.28, p < 0.0001; miR-133a-3p: 2.09 ± 0.10 vs. 0.74 ± 0.11 mean ± SD, p = 0.0002). Conversely, in lvPPA, the majority of miRNAs were downregulated. GO enrichment and KEGG pathway analyses revealed that target genes of both miRNAs are involved in pathways potentially relevant for the pathogenesis of neurodegenerative diseases. This is the first study that investigates the expression profile of circulating miRNAs in PPA variant patients. We identified a specific miRNA expression profile in svPPA that could differentiate this pathological condition from other PPA variants. Nevertheless, these preliminary results need to be confirmed in a larger independent cohort. Full article
(This article belongs to the Special Issue Multifaceted and Diversified Roles of MicroRNAs in Health, Diseases and Death)
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Review

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14 pages, 264 KiB  
Review
An Overview on the Use of miRNAs as Possible Forensic Biomarkers for the Diagnosis of Traumatic Brain Injury
by Giuseppe Davide Albano, Chiara Stassi, Antonina Argo and Stefania Zerbo
Int. J. Mol. Sci. 2023, 24(7), 6503; https://doi.org/10.3390/ijms24076503 - 30 Mar 2023
Cited by 1 | Viewed by 1245
Abstract
Determining the cause of death is one of the main goals of forensic pathology. However, conditions can occur in which common approaches—external inspection, autopsy, histology, etc.—might not be conclusive. With the advancement of molecular biology, several investigative techniques have been developed over the [...] Read more.
Determining the cause of death is one of the main goals of forensic pathology. However, conditions can occur in which common approaches—external inspection, autopsy, histology, etc.—might not be conclusive. With the advancement of molecular biology, several investigative techniques have been developed over the years, and the application as approaches complementary to routine procedures has proved useful in these cases. In this context, microRNA (miRNA) profiling has attracted increasing interest due to these molecules’ ability to regulate physiological and pathological processes. The evidence of differential miRNA expression in both animal models and human samples of traumatic brain injury (TBI) has laid the basis for comprehension of the underlying pathophysiological mechanisms, thus allowing us to identify some of them as possible TBI diagnostic biomarkers. The present narrative review aims to explore the primary miRNAs involved in the mechanisms underlying TBI, which could be considered for future evaluation as possible markers in a post mortem setting. Full article
(This article belongs to the Special Issue Multifaceted and Diversified Roles of MicroRNAs in Health, Diseases and Death)
19 pages, 1104 KiB  
Review
miRNA Dysregulation in Cardiovascular Diseases: Current Opinion and Future Perspectives
by Francesco Sessa, Monica Salerno, Massimiliano Esposito, Giuseppe Cocimano and Cristoforo Pomara
Int. J. Mol. Sci. 2023, 24(6), 5192; https://doi.org/10.3390/ijms24065192 - 08 Mar 2023
Cited by 12 | Viewed by 2192
Abstract
MicroRNAs (miRNAs), small noncoding RNAs, are post-transcriptional gene regulators that can promote the degradation or decay of coding mRNAs, regulating protein synthesis. Many experimental studies have contributed to clarifying the functions of several miRNAs involved in regulatory processes at the cardiac level, playing [...] Read more.
MicroRNAs (miRNAs), small noncoding RNAs, are post-transcriptional gene regulators that can promote the degradation or decay of coding mRNAs, regulating protein synthesis. Many experimental studies have contributed to clarifying the functions of several miRNAs involved in regulatory processes at the cardiac level, playing a pivotal role in cardiovascular disease (CVD). This review aims to provide an up-to-date overview, with a focus on the past 5 years, of experimental studies on human samples to present a clear background of the latest advances to summarize the current knowledge and future perspectives. SCOPUS and Web of Science were searched using the following keywords: (miRNA or microRNA) AND (cardiovascular diseases); AND (myocardial infarction); AND (heart damage); AND (heart failure), including studies published from 1 January 2018 to 31 December 2022. After an accurate evaluation, 59 articles were included in the present systematic review. While it is clear that miRNAs are powerful gene regulators, all the underlying mechanisms remain unclear. The need for up-to-date data always justifies the enormous amount of scientific work to increasingly highlight their pathways. Given the importance of CVDs, miRNAs could be important both as diagnostic and therapeutic (theranostic) tools. In this context, the discovery of “TheranoMIRNAs” could be decisive in the near future. The definition of well-setout studies is necessary to provide further evidence in this challenging field. Full article
(This article belongs to the Special Issue Multifaceted and Diversified Roles of MicroRNAs in Health, Diseases and Death)
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