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Journal of Clinical Medicine Jun 2024Recurrent pregnancy loss refers to the spontaneous demise of two or more pregnancies before the 24 weeks of gestation. In almost half of the cases of recurrent... (Review)
Review
Recurrent pregnancy loss refers to the spontaneous demise of two or more pregnancies before the 24 weeks of gestation. In almost half of the cases of recurrent miscarriages, the causes remain unknown since there is no reliable way of prognosis, early diagnosis, or treatment. Recent research has detected differential expression of certain miRNAs in reproductive system pathologies. The aim of the present review is to focus on microRNAs and their relationship with idiopathic recurrent miscarriages and to correlate miRNA expression with recurrent miscarriage and examine their potential role as biomarkers. Pubmed/Medline and Scopus databases were searched up to 31st January 2024 with terms related to recurrent pregnancy loss and miRNAs. In total, 21 studies were selected for the review. A total of 75 different miRNAs were identified, showing a statistically significant differential expression. Around 40 miRNAs had increased expression, such as miR-520, miR-184 and miR-100-5p, 21 decreased, such as let-7c, and 14 had either increased or decreased expression depending on the study, such as miR-21. The dysregulation of miRNA expression is strongly associated with recurrent miscarriages. The circulating in the peripheral blood miRNAs, miR-100-5p and let-7c, might be utilized as biomarkers and establish a valuable non-invasive prognostic and diagnostic tool in the future.
PubMed: 38929888
DOI: 10.3390/jcm13123361 -
Journal of Personalized Medicine May 2024Direct oral anticoagulants (DOACs) are the standard treatment for thromboembolic protection in atrial fibrillation (AF) patients. Epigenetic modifications, such as DNA...
Circulating microRNAs and DNA Methylation as Regulators of Direct Oral Anticoagulant Response in Atrial Fibrillation and Key Elements for the Identification of the Mechanism of Action (miR-CRAFT): Study Design and Patient Enrolment.
Direct oral anticoagulants (DOACs) are the standard treatment for thromboembolic protection in atrial fibrillation (AF) patients. Epigenetic modifications, such as DNA methylation and microRNAs, have emerged as potential biomarkers of AF. The epigenetics of DOACs is still an understudied field. It is largely unknown whether epigenetic modifications interfere with DOAC response or whether DOAC treatment induces epigenetic modifications. To fill this gap, we started the miR-CRAFT (Circulating microRNAs and DNA methylation as regulators of Direct Oral Anticoagulant Response in Atrial Fibrillation) research study. In miR-CRAFT, we follow, over time, changes in DNA methylation and microRNAs expression in naïve AF patients starting DOAC treatment. The ultimate goal of miR-CRAFT is to identify the molecular pathways epigenetically affected by DOACs, beyond the coagulation cascade, that are potentially mediating DOAC pleiotropic actions and to propose specific microRNAs as novel circulating biomarkers for DOAC therapy monitoring. We herein describe the study design and briefly present the progress in participant enrolment.
PubMed: 38929783
DOI: 10.3390/jpm14060562 -
Life (Basel, Switzerland) Jun 2024Expression of microRNAs, such as miR-365, is known to be dysregulated in many tumors, including oral cancers, although little is known about their role or functions. The...
Expression of microRNAs, such as miR-365, is known to be dysregulated in many tumors, including oral cancers, although little is known about their role or functions. The objective of this project is to evaluate the downstream targets of miR-365 to determine any potential pathways or effects. Downstream targets for miR-365 (miRdatabase target scores > 90) were used for qPCR screening of oral cancer cell lines (SCC4, SCC9, SCC15, SCC25, CAL27). Each oral cancer cell line expressed miR-365 downstream targets molybdenum cofactor synthesis-2 (MOCS2), erythropoietin receptor (EPOR), IQ motif containing-K (IQCK), carboxypeptidase A3 (CPA3), solute carrier family 24 member-3 (SLC24A3), and coiled-coil domain containing 47 (CCDC47)-although the expression levels varied somewhat. However, differential results were observed with ubiquitin protein ligase E3 component n-recognin-3 (UBR3), nudix hydrolase-12 (NUDT12), zinc finger CCHC-type containing-14 (ZCCHC14), and homeobox and leucine zipper encoding (HOMEZ). These data suggest that many of the miR-365 targets are expressed in the oral cancers screened, with the differential expression of UBR3, ZCCHC14, HOMEZ, and NUDT12, which may be correlated with chemoresistance among two specific oral cancer cell lines (SCC25, SCC9). These results suggest this differential expression may signal potential targets for patient treatment with tumors exhibiting miR-365 and chemotherapeutic resistance.
PubMed: 38929724
DOI: 10.3390/life14060741 -
Life (Basel, Switzerland) May 2024Glioblastoma (GB) is the most common and most aggressive primary brain tumor in adults, with an overall survival almost 14.6 months. Optimal resection followed by... (Review)
Review
Glioblastoma (GB) is the most common and most aggressive primary brain tumor in adults, with an overall survival almost 14.6 months. Optimal resection followed by combined temozolomide chemotherapy and radiotherapy, also known as Stupp protocol, remains the standard of treatment; nevertheless, resistance to temozolomide, which can be obtained throughout many molecular pathways, is still an unsurpassed obstacle. Several factors influence the efficacy of temozolomide, including the involvement of other DNA repair systems, aberrant signaling pathways, autophagy, epigenetic modifications, microRNAs, and extracellular vesicle production. The blood-brain barrier, which serves as both a physical and biochemical obstacle, the tumor microenvironment's pro-cancerogenic and immunosuppressive nature, and tumor-specific characteristics such as volume and antigen expression, are the subject of ongoing investigation. In this review, preclinical and clinical data about temozolomide resistance acquisition and possible ways to overcome chemoresistance, or to treat gliomas without restoration of chemosensitinity, are evaluated and presented. The objective is to offer a thorough examination of the clinically significant molecular mechanisms and their intricate interrelationships, with the aim of enhancing understanding to combat resistance to TMZ more effectively.
PubMed: 38929657
DOI: 10.3390/life14060673 -
Antioxidants (Basel, Switzerland) Jun 2024Many countries, including Japan, are experiencing declining birth rates. Assisted reproductive technologies have consistently demonstrated good results in resolving...
Transwell Culture with Adipose Tissue-Derived Stem Cells and Fertilized Eggs Mimics the In Vivo Development of Fertilized Eggs to Blastocysts in the Fallopian Tube: An Animal Study.
Many countries, including Japan, are experiencing declining birth rates. Assisted reproductive technologies have consistently demonstrated good results in resolving infertility. Although the development of fertilized eggs into blastocysts has been recognized as a crucial step in assisted reproductive technologies, the involved mechanisms are currently unclear. Here, we established a new culture system for the in vitro development of fertilized eggs into blastocysts. In the Transwell culture system, the rate of blastocysts hatching from fertilized eggs cultured with adipose-derived stem cells (ASCs) was significantly higher than that of blastocysts cultured only with fertilized eggs. Gene ontology analysis revealed that the developed blastocysts displayed essential gene expression patterns in mature blastocysts. Additionally, when cultured with 3rd-passage ASCs, the developed blastocysts expressed the core genes for blastocyst maturation and antioxidant properties compared to those cultured only with fertilized eggs or cultured with 20th-passage ASCs. These results suggest that the Transwell culture system may imitate the in vivo tubal culture state for fertilized eggs. Exosomes derived from stem cells with stemness potential play a powerful role in the development of blastocysts from fertilized eggs. Additionally, the exosomes expressed specific microRNAs; therefore, the Transwell culture system resulted in a higher rate of pregnancy. In future, the extraction of their own extracellular vesicles from the culture medium might contribute to the development of novel assisted reproductive technologies.
PubMed: 38929143
DOI: 10.3390/antiox13060704 -
Antioxidants (Basel, Switzerland) May 2024Ischemic conditionings (ICon) were intensively investigated and several protective signaling pathways were identified. Previously, we have shown the role of matrix...
INTRODUCTION
Ischemic conditionings (ICon) were intensively investigated and several protective signaling pathways were identified. Previously, we have shown the role of matrix metalloproteinases (MMP) in myocardial ischemia/reperfusion injury (MIRI) and the cardioprotective role of biglycan (BGN), a small leucine-rich proteoglycan in vitro. Here, we hypothesized that cardiac MMP and BGN signaling are involved in the protective effects of ICon.
METHODS
A reverse target-microRNA prediction was performed by using the miRNAtarget™ 2.0 software to identify human microRNAs with a possible regulatory effect on MMP and BGN, such as on related genes. To validate the identified 1289 miRNAs in the predicted network, we compared them to two cardioprotective miRNA omics datasets derived from pig and rat models of MIRI in the presence of ICons.
RESULTS
Among the experimentally measured miRNAs, we found 100% sequence identity to human predicted regulatory miRNAs in the case of 37 porcine and 24 rat miRNAs. Upon further analysis, 42 miRNAs were identified as MIRI-associated miRNAs, from which 24 miRNAs were counter-regulated due to ICons.
CONCLUSIONS
Our findings highlight 24 miRNAs that potentially regulate cardioprotective therapeutic targets associated with MMPs and BGN in a highly translatable porcine model of acute myocardial infarction.
PubMed: 38929113
DOI: 10.3390/antiox13060674 -
Antioxidants (Basel, Switzerland) May 2024MicroRNAs (miRNAs) have been highlighted as key players in numerous diseases, and accumulating evidence indicates that pathological expressions of miRNAs contribute to... (Review)
Review
MicroRNAs (miRNAs) have been highlighted as key players in numerous diseases, and accumulating evidence indicates that pathological expressions of miRNAs contribute to both the development and progression of cardiovascular diseases (CVD), as well. Another important factor affecting the development and progression of CVD is reactive oxygen species (ROS), as well as the oxidative stress they may impose on the cells. Considering miRNAs are involved in virtually every biological process, it is not unreasonable to assume that miRNAs also play critical roles in the regulation of oxidative stress. This narrative review aims to provide mechanistic insights on possible oxidative stress-regulating roles of miRNAs in cardiovascular diseases based on differentially expressed miRNAs reported in various cardiovascular diseases and their empirically validated targets that have been implicated in the regulation of oxidative stress.
PubMed: 38929095
DOI: 10.3390/antiox13060656 -
International Journal of Molecular... Jun 2024Brace root architecture is a critical determinant of maize's stalk anchorage and nutrition uptake, influencing root lodging resistance, stress tolerance, and plant...
Brace root architecture is a critical determinant of maize's stalk anchorage and nutrition uptake, influencing root lodging resistance, stress tolerance, and plant growth. To identify the key microRNAs (miRNAs) in control of maize brace root growth, we performed small RNA sequencing using brace root samples at emergence and growth stages. We focused on the genetic modulation of brace root development in maize through manipulation of miR390 and its downstream regulated (). In the present study, miR167, miR166, miR172, and miR390 were identified to be involved in maize brace root growth in inbred line B73. Utilizing short tandem target mimic (STTM) technology, we further developed maize lines with reduced miR390 expression and analyzed their root architecture compared to wild-type controls. Our findings show that maize lines exhibit enhanced brace root length and increased whorl numbers. Gene expression analyses revealed that the suppression of miR390 leads to upregulation of its downstream regulated ARF genes, specifically and , which may significantly alter root architecture. Additionally, loss-of-function mutants for and were characterized to further confirm the role of these genes in brace root growth. These results demonstrate that miR390, , and play crucial roles in regulating maize brace root growth; the involved complicated molecular mechanisms need to be further explored. This study provides a genetic basis for breeding maize varieties with improved lodging resistance and adaptability to diverse agricultural environments.
Topics: Zea mays; MicroRNAs; Plant Roots; Gene Expression Regulation, Plant; Plant Proteins; Gene Knockdown Techniques
PubMed: 38928499
DOI: 10.3390/ijms25126791 -
International Journal of Molecular... Jun 2024Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress and inflammatory factors, among others, and these are targets for...
Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation (inflamma-miRs), including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR). A differential expression profile of miRNs was detected in untreated MDS patients and the 5-AZA group. Inflammation increases miRNs and, specifically, miR-18a, miR-21 and miR-34a were significantly overexpressed in untreated MDS, compared to controls. However, we did not observe any miRN profile alteration during the progression of the disease. On the other hand, 5-AZA treatment tends to restore miRN expression levels. Relating to prognostic risk factors, high-risk MDS groups (high Revised International Prognostic Scoring System (IPSS-R), high cytogenetic risk, high molecular risk (HMR) mutations) tended to be related with higher expression levels of miR-18a and miR-34a. Higher miRN expression is correlated with lower glutathione peroxidase activity, while they are related with a higher profile of pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α). Although our study was limited by the low number of MDS patients included, we identified miRN deregulation involved in MDS development that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRN expression levels in MDS patients.
Topics: Humans; Myelodysplastic Syndromes; MicroRNAs; Male; Female; Middle Aged; Aged; Inflammation; Azacitidine; Adult; Aged, 80 and over; Oxidative Stress; Case-Control Studies; Prognosis
PubMed: 38928489
DOI: 10.3390/ijms25126784 -
International Journal of Molecular... Jun 2024Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study...
Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study explored the utility of circulating microRNAs encapsulated in extracellular vesicles (EV-miRNAs) to distinguish the following ischemic stroke subtypes: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and small artery occlusion (SAO). Using next-generation sequencing (NGS) and machine-learning techniques, we identified differentially expressed miRNAs (DEMs) associated with each subtype. Through patient selection and diagnostic evaluation, a cohort of 70 patients with acute ischemic stroke was classified: 24 in the LAA group, 24 in the SAO group, and 22 in the CES group. Our findings revealed distinct EV-miRNA profiles among the groups, suggesting their potential as diagnostic markers. Machine-learning models, particularly logistic regression models, exhibited a high diagnostic accuracy of 92% for subtype discrimination. The collective influence of multiple miRNAs was more crucial than that of individual miRNAs. Additionally, bioinformatics analyses have elucidated the functional implications of DEMs in stroke pathophysiology, offering insights into the underlying mechanisms. Despite limitations like sample size constraints and retrospective design, our study underscores the promise of EV-miRNAs coupled with machine learning for ischemic stroke subtype classification. Further investigations are warranted to validate the clinical utility of the identified EV-miRNA biomarkers in stroke patients.
Topics: Humans; Machine Learning; Ischemic Stroke; Male; Circulating MicroRNA; Female; Aged; Middle Aged; Exosomes; Biomarkers; High-Throughput Nucleotide Sequencing; Computational Biology; MicroRNAs; Gene Expression Profiling; Extracellular Vesicles
PubMed: 38928481
DOI: 10.3390/ijms25126761