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Cell-Free Nucleic Acids in the Molecular Pathogenesis of Diseases Development 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 16099

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Special Issue Editor

Prof. Dr. Bálint Nagy

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Guest Editor

Department of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
Interests: comparison of nucleic acid isolation methods; cell-free nucleic acid isolation; gene expression measurement; clinical application of liquid biopsy; diagnosis of genetic diseases; cell-free gDNA; mtDNA; miRNA and lncRNA studies in oncological and cardiovascular diseases; exosome isolation methods; nucleic acid measurements from exosomes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cell-free nucleic acids (DNA, mitochondrial DNA, microRNA, long non-coding RNA, circular RNA), which are released by cells to different body fluids via active transport or by apoptosis or necrosis in both normal and pathological conditions, have been the focus of recent research. They are considered to be biomarkers for detection and molecular classification of samples obtained from patients having cancer, stroke, myocardial infarction, diabetes, sepsis, etc. Liquid biopsy has recently become a very popular sampling procedure for such purposes. The main advantage of this method is the possibility of easy and repetitive obtaining of samples. Cell-free nucleic acid can be isolated from bloody fluids in a short time. Their use in diagnostic or screening processes is already accepted. They also provide the possibility to follow up patients’ treatments. Liquid biopsy is applicable during the diagnosis of oncological, cardiovascular, neurological, and infectious diseases, among others. Gene expression studies could provide valuable information to researchers and clinicians. Currently, it seems promising to isolate exosomes from liquid biopsies and understand their role in the development of pathological conditions. We can collect valuable information on cell–cell–tissue communication. Identification of new extra- and intracellular signaling nucleic acid molecules and finding out their pathways could help in the diagnosis and treatment of patients.

Cell-free DNA is already widely used in the prenatal detection of genetic diseases. Recently, oncological diseases have been the focus of research, and the newest area of research is cardiovascular and neurological diseases using regulator RNA molecules.

Therefore, authors are invited to submit original research and review articles that address the progress and current standing of cell-free nucleic acids to understand the molecular pathology of diseases and develop biomarkers for screening and follow up.

Topics include, but are not limited to, the following:

Gene expression studies of diseases using cell-free nucleic acids;
Gene mutation studies;
Application of cell-free nucleic acids such as biomarkers in different types of diseases;
Techniques for isolation, detection, analysis, and identification of signaling nucleic acid molecules, pathways, and networks;
Standardization of related protocols.

Prof. Bálint Nagy
Guest Editor

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

cell-free nucleic acids
liquid biopsy
biomarkers
non-invasive
exosomes

Published Papers (6 papers)

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Research

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7 pages, 710 KiB

Open AccessCommunication

Endogenous DNase Activity in an Animal Model of Acute Liver Failure

by Ľubica Janovičová, Katarína Kmeťová, Nikola Pribulová, Jakub Janko, Barbora Gromová, Roman Gardlík and Peter Celec

Int. J. Mol. Sci. 2023, 24(3), 2984; https://doi.org/10.3390/ijms24032984 - 3 Feb 2023

Cited by 1 | Viewed by 1624

Abstract

Deoxyribonucleases (DNases) cleave extracellular DNA (ecDNA) and are under intense research as interventions for diseases associated with high ecDNA, such as acute live injury. DNase I treatment decreases morbidity and mortality in this animal model. Endogenous DNase activity has high interindividual variability. In this study, we tested the hypothesis that high endogenous DNase activity is beneficial in an animal model of acute liver failure. DNase activity was measured in the plasma of adult male mice taken before i.p. injection of thioacetamide to induce acute liver failure. The survival of mice was monitored for 48 h. Mice were retrospectively divided into two groups based on the median DNase activity assessed using the gel-based single-radial enzyme diffusion assay. In acute liver failure, mice with a higher baseline DNase activity had lower mortality after 48 h (by 25%). Different protection of ecDNA against nucleases by vesicles or DNA-binding proteins could play a role and should be further evaluated. Similarly, the role of endogenous DNase activity should be analyzed in other disease models associated with high ecDNA. Full article

(This article belongs to the Special Issue Cell-Free Nucleic Acids in the Molecular Pathogenesis of Diseases Development 2.0)

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17 pages, 2585 KiB

Open AccessArticle

Psoriasis-Associated Inflammatory Conditions Induce IL-23 mRNA Expression in Normal Human Epidermal Keratinocytes

by Evelyn Kelemen, Éva Ádám, Stella Márta Sági, Anikó Göblös, Lajos Kemény, Zsuzsanna Bata-Csörgő, Márta Széll and Judit Danis

Int. J. Mol. Sci. 2022, 23(1), 540; https://doi.org/10.3390/ijms23010540 - 4 Jan 2022

Cited by 2 | Viewed by 2052

Abstract

Psoriasis is a multifactorial, chronic inflammatory skin disease, the development of which is affected by both genetic and environmental factors. Cytosolic nucleic acid fragments, recognized as pathogen- and danger-associated molecular patterns, are highly abundant in psoriatic skin. It is known that psoriatic skin exhibits increased levels of IL-23 compared to healthy skin. However, the relationship between free nucleic acid levels and IL-23 expression has not been clarified yet. To examine a molecular mechanism by which nucleic acids potentially modulate IL-23 levels, an in vitro system was developed to investigate the IL-23 mRNA expression of normal human epidermal keratinocytes under psoriasis-like circumstances. This system was established using synthetic nucleic acid analogues (poly(dA:dT) and poly(I:C)). Signaling pathways, receptor involvement and the effect of PRINS, a long non-coding RNA previously identified and characterized by our research group, were analyzed to better understand the regulation of IL-23 in keratinocytes. Our results indicate that free nucleic acids regulate epithelial IL-23 mRNA expression through the TLR3 receptor and specific signaling pathways, thereby, contributing to the development of an inflammatory milieu favorable for the appearance of psoriatic symptoms. A moderate negative correlation was confirmed between the nucleic-acid-induced IL-23 mRNA level and the rate of its decrease upon PRINS overexpression. Full article

(This article belongs to the Special Issue Cell-Free Nucleic Acids in the Molecular Pathogenesis of Diseases Development 2.0)

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17 pages, 3672 KiB

Open AccessArticle

Circulatory Neutrophils Exhibit Enhanced Neutrophil Extracellular Trap Formation in Early Puerperium: NETs at the Nexus of Thrombosis and Immunity

by Stavros Giaglis, Chanchal Sur Chowdhury, Shane Vontelin van Breda, Maria Stoikou, André N. Tiaden, Douglas Daoudlarian, Guenther Schaefer, Andreas Buser, Ulrich A. Walker, Olav Lapaire, Irene Hoesli, Paul Hasler and Sinuhe Hahn

Int. J. Mol. Sci. 2021, 22(24), 13646; https://doi.org/10.3390/ijms222413646 - 20 Dec 2021

Cited by 4 | Viewed by 2522

Abstract

Pregnancy is associated with elevated maternal levels of cell-free DNA of neutrophil extracellular trap (NET) origin, as circulatory neutrophils exhibit increased spontaneous NET formation, mainly driven by G-CSF and finely modulated by sex hormones. The postpartum period, on the other hand, involves physiological alterations consistent with the need for protection against infections and fatal haemorrhage. Our findings indicate that all relevant serum markers of neutrophil degranulation and NET release are substantially augmented postpartum. Neutrophil pro-NETotic activity in vitro is also upregulated particularly in post-delivery neutrophils. Moreover, maternal puerperal neutrophils exhibit a strong pro-NETotic phenotype, associated with increased levels of all key players in the generation of NETs, namely citH3, MPO, NE, and ROS, compared to non-pregnant and pregnant controls. Intriguingly, post-delivery NET formation is independent of G-CSF in contrast to late gestation and complemented by the presence of TF on the NETs, alterations in the platelet activity status, and activation of the coagulation cascade, triggered by circulating microparticles. Taken together, our results reveal the highly pro-NETotic and potentially procoagulant nature of postpartum neutrophils, bridging an overt immune activation with possible harmful thrombotic incidence. Full article

(This article belongs to the Special Issue Cell-Free Nucleic Acids in the Molecular Pathogenesis of Diseases Development 2.0)

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20 pages, 4365 KiB

Open AccessArticle

Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells

by Zsolt Fejes, Marianna Pócsi, Jun Takai, Judit Erdei, Andrea Tóth, Enikő Balogh, Ágnes Rusznyák, Ferenc Fenyvesi, Andrea Nagy, János Kappelmayer, Viktória Jeney and Béla Nagy, Jr.

Int. J. Mol. Sci. 2021, 22(16), 8648; https://doi.org/10.3390/ijms22168648 - 11 Aug 2021

Cited by 13 | Viewed by 2272

Abstract

Following an intraventricular hemorrhage (IVH), red blood cell lysis and hemoglobin (Hb) oxidation with the release of heme can cause sterile neuroinflammation. In this study, we measured Hb derivates and cellular adhesion molecules ICAM-1 and VCAM-1 with cell-free miRNAs in cerebrospinal fluid (CSF) samples obtained from Grade-III and Grade-IV preterm IVH infants (IVH-III and IVH-IV, respectively) at multiple time points between days 0–60 after the onset of IVH. Furthermore, human choroid plexus epithelial cells (HCPEpiCs) were incubated with IVH and non-IVH CSF (10 v/v %) for 24 h in vitro to investigate the IVH-induced inflammatory response that was investigated via: (i) HMOX1, IL8, VCAM1, and ICAM1 mRNAs as well as miR-155, miR-223, and miR-181b levels by RT-qPCR; (ii) nuclear translocation of the NF-κB p65 subunit by fluorescence microscopy; and (iii) reactive oxygen species (ROS) measurement. We found a time-dependent alteration of heme, IL-8, and adhesion molecules which revealed a prolonged elevation in IVH-IV vs. IVH-III with higher miR-155 and miR-181b expression at days 41–60. Exposure of HCPEpiCs to IVH CSF samples induced HMOX1, IL8, and ICAM1 mRNA levels along with increased ROS production via the NF-κB pathway activation but without cell death, as confirmed by the cell viability assay. Additionally, the enhanced intracellular miR-155 level was accompanied by lower miR-223 and miR-181b expression in HCPEpiCs after CSF treatment. Overall, choroid plexus epithelial cells exhibit an abnormal cell phenotype after interaction with pro-inflammatory CSF of IVH origin which may contribute to the development of later clinical complications in preterm IVH. Full article

(This article belongs to the Special Issue Cell-Free Nucleic Acids in the Molecular Pathogenesis of Diseases Development 2.0)

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Review

Jump to: Research

21 pages, 1831 KiB

Open AccessReview

Cross-Kingdom Interaction of miRNAs and Gut Microbiota with Non-Invasive Diagnostic and Therapeutic Implications in Colorectal Cancer

by Ondrej Pös, Jakub Styk, Gergely Buglyó, Michal Zeman, Lydia Lukyova, Kamila Bernatova, Evelina Hrckova Turnova, Tomas Rendek, Ádám Csók, Vanda Repiska, Bálint Nagy and Tomas Szemes

Int. J. Mol. Sci. 2023, 24(13), 10520; https://doi.org/10.3390/ijms241310520 - 23 Jun 2023

Cited by 1 | Viewed by 1985

Abstract

Colorectal cancer (CRC) has one of the highest incidences among all types of malignant diseases, affecting millions of people worldwide. It shows slow progression, making it preventable. However, this is not the case due to shortcomings in its diagnostic and management procedure and a lack of effective non-invasive biomarkers for screening. Here, we discuss CRC-associated microRNAs (miRNAs) and gut microbial species with potential as CRC diagnostic and therapy biomarkers. We provide rich evidence of cross-kingdom miRNA-mediated interactions between the host and gut microbiome. miRNAs have emerged with the ability to shape the composition and dynamics of gut microbiota. Intestinal microbes can uptake miRNAs, which in turn influence microbial growth and provide the ability to regulate the abundance of various microbial species. In the context of CRC, targeting miRNAs could aid in manipulating the balance of the microbiota. Our findings suggest the need for correlation analysis between the composition of the gut microbiome and the miRNA expression profile. Full article

(This article belongs to the Special Issue Cell-Free Nucleic Acids in the Molecular Pathogenesis of Diseases Development 2.0)

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19 pages, 713 KiB

Open AccessReview

The Role of Exosomes in Cancer Progression

by Beáta Soltész, Gergely Buglyó, Nikolett Németh, Melinda Szilágyi, Ondrej Pös, Tomas Szemes, István Balogh and Bálint Nagy

Int. J. Mol. Sci. 2022, 23(1), 8; https://doi.org/10.3390/ijms23010008 - 21 Dec 2021

Cited by 21 | Viewed by 4744

Abstract

Early detection, characterization and monitoring of cancer are possible by using extracellular vesicles (EVs) isolated from non-invasively obtained liquid biopsy samples. They play a role in intercellular communication contributing to cell growth, differentiation and survival, thereby affecting the formation of tumor microenvironments and causing metastases. EVs were discovered more than seventy years ago. They have been tested recently as tools of drug delivery to treat cancer. Here we give a brief review on extracellular vesicles, exosomes, microvesicles and apoptotic bodies. Exosomes play an important role by carrying extracellular nucleic acids (DNA, RNA) in cell-to-cell communication causing tumor and metastasis development. We discuss the role of extracellular vesicles in the pathogenesis of cancer and their practical application in the early diagnosis, follow up, and next-generation treatment of cancer patients. Full article

(This article belongs to the Special Issue Cell-Free Nucleic Acids in the Molecular Pathogenesis of Diseases Development 2.0)

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