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Journal of Diabetes and Metabolic... Jun 2024Diabetes mellitus [DM], is a multifaceted metabolic disease, which has become a worldwide threat to human wellness. Over the past decades, an enormous amount of... (Review)
Review
OBJECTIVES
Diabetes mellitus [DM], is a multifaceted metabolic disease, which has become a worldwide threat to human wellness. Over the past decades, an enormous amount of attention has been devoted to understanding how microRNAs [miRNAs], a class of small non-coding RNA regulators of gene expression at the post-transcriptional level, are tied to DM pathology. It has been demonstrated that miRNAs control insulin synthesis, secretion, and activity. This review aims to provide an evaluation of the use of miR-143 and miR-145 as biomarkers for the diagnosis and prognosis of diabetes.
METHODS
The use of miR-143 and miR-145 as biomarkers for the diagnosis and prognosis of diabetes has been studied, and research that examined this link was sought after in the literature. In addition, we will discuss the cellular and molecular pathways of insulin secretion regulation by miR-143/145 expression and finally their role in diabetes.
RESULTS
In the current review, we emphasize recent findings on the miR-143/145 expression profiles as novel DM biomarkers in clinical studies and animal models and highlight recent discoveries on the complex regulatory effect and functional role of miR-143/145 expression in DM.
CONCLUSION
A novel clinical treatment that alters the expression and activity of miR-143/miR-145 may be able to return cells to their natural state of glucose homeostasis, demonstrating the value of using comprehensive miRNA profiles to predict the beginning of diabetes.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-023-01317-y.
PubMed: 38932869
DOI: 10.1007/s40200-023-01317-y -
Journal of Diabetes and Metabolic... Jun 2024MicroRNAs (miRNAs, miRs) have been linked to beta-cell pathologies and have also shown potential as biomarkers for cardiovascular disease. This study aimed to evaluate...
BACKGROUND
MicroRNAs (miRNAs, miRs) have been linked to beta-cell pathologies and have also shown potential as biomarkers for cardiovascular disease. This study aimed to evaluate the expression of miR-375 and miR-541 in T2D patients with and without CAD, in order to determine the potential of these miRNAs as biomarkers for assessing CAD risk.
METHODS
This study was conducted on 106 patients with T2D who underwent coronary angiographic examination. Reverse transcription was performed using the cDNA synthesis kit. Real-time PCR was performed using the SYBR Green method and specific primers. The ability to predict which person had developed CAD was evaluated by calculating the area under the receiver-operating characteristic (ROC) curve (AUC).
RESULTS
The expression of miR-375 was significantly higher in samples from CAD patients compared to those without CAD ( = 0.009). While the expression of miR-541 was also higher in CAD patients, the difference was not statistically significant. In terms of predicting CAD, miR-375 was found to be a suitable predictor with an AUC of 0.74 ( = 0.01), while miR-541 was not. With a cut-off value of 0.016 for miR-375, the sensitivity was 67% and the specificity was 80%.
CONCLUSION
Our results indicated that circulating levels of miR-375 and miR-541 were elevated in T2D patients with CAD compared to those without CAD. This suggests that miR-375 could potentially be used as a non-invasive biomarker for the diagnosis of CAD in T2D patients.
PubMed: 38932834
DOI: 10.1007/s40200-024-01391-w -
Journal of Diabetes and Metabolic... Jun 2024To investigate the potential relation between methylation of miR-9-3 and stages of diabetic retinopathy (DR). Additionally, we explored whether miR-9-3 methylation...
PURPOSE
To investigate the potential relation between methylation of miR-9-3 and stages of diabetic retinopathy (DR). Additionally, we explored whether miR-9-3 methylation impacts the serum levels of Vascular Endothelial Growth Factor (VEGF).
METHODS
A cross-sectional study was conducted with 170 participants with type 2 diabetes, including a control group ( = 64) and a diabetes retinopathy group ( = 106), which was further divided into NPDR ( = 58) and PDR ( = 48) subgroups. Epidemiological, clinical, anthropometric, biochemical ELISA assay were analysed. DNA extracted from leukocytes was used to profile miR-9-3 methylation using PCR-MSP.
RESULTS
MiR-9-3 hypermethylated profile was higher in the DR group ( < 0.001) and PDR subgroup compared to DM2 control group ( < 0.001). The hypermethylated profile in the PDR subgroup was also higher compared to NPDR subgroup ( < 0.001). There was no difference between DM2 control and NPDR group ( = 0.234). Logistic regression showed that miR-9-3 hypermethylation increases the odds of presenting DR (OR: 2.826; = 0.002) and PDR (OR: 5.472; < 0.001). In addition, hypermethylation of miR-9-3 in the DR and NPDR subgroup was associated with higher serum VEGF-A levels ( = 0.012 and = 0.025, respectively).
CONCLUSION
The methylation profile of the miR-9-3 promoter increases the risk of developing PDR. Higher levels of VEGF-A are associated with miR-9-3 hypermethylated profile in patients in the DR and NPDR stages.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-024-01411-9.
PubMed: 38932799
DOI: 10.1007/s40200-024-01411-9 -
Journal of Applied Physiology... Jun 2024Resistance training (RT) remains the most effective treatment for age-related declines in muscle mass. However, many older adults experience attenuated muscle...
Resistance training (RT) remains the most effective treatment for age-related declines in muscle mass. However, many older adults experience attenuated muscle hypertrophy in response to RT when compared to younger adults. This may be attributed to underlying molecular processes that are dysregulated by aging and exacerbated by improperly prescribed RT weekly volume, intensity, and/or frequency doses. MicroRNA (miRNA) are key epigenetic regulators that impact signaling pathways and protein expression within cells, are dynamic and responsive to exercise stimuli, and are often dysregulated in diseases. In this study, we used untargeted miRNA-seq to examine miRNA in skeletal muscle and serum-derived exosomes of older adults (n = 18, 11M/7F, 66±1y) who underwent 3x/wk RT for 30 weeks [e.g., high intensity 3x/wk (HHH, n = 9) or alternating high-low-high intensity (HLH, n = 9)], after a standardized four-week wash-in. Within each tissue, miRNAs were clustered into modules based on pairwise correlation using Weighted Gene Correlation Network Analysis (WGCNA). Modules were tested for association with the magnitude of RT-induced thigh lean mass (TLM) change (as measured by DXA). While no modules were unique to training dose, we identified miRNA modules in skeletal muscle associated with TLM gains irrespective of exercise dose. Using miRNA-target interactions, we analyzed key miRNAs in significant modules for their potential regulatory involvement in biological pathways. Findings point toward potential miRNAs that may be informative biomarkers and could also be evaluated as potential therapeutic targets as an adjuvant to RT in order to maximize skeletal muscle mass accrual in older adults.
PubMed: 38932684
DOI: 10.1152/japplphysiol.00680.2023 -
Vaccines Jun 2024The impact of mRNA COVID-19 vaccines on the immunological profiles of pregnant women remains a crucial area of study. This research aims to explore the specific...
BACKGROUND
The impact of mRNA COVID-19 vaccines on the immunological profiles of pregnant women remains a crucial area of study. This research aims to explore the specific immunological changes triggered by these vaccines in this demographic.
METHODS
In a focused investigation, we examined the effects of mRNA COVID-19 vaccination on microRNA expression in pregnant women. Key microRNAs, including miR-451a, miR-23a-3p, and miR-21-5p, were analyzed for expression changes post-vaccination. Additionally, we assessed variations in S1RBD IgG levels and specific cytokines to gauge the broader immunological response.
RESULTS
Post-vaccination, significant expression shifts in the targeted microRNAs were observed. Alongside these changes, we noted alterations in S1RBD IgG and various cytokines, indicating an adapted inflammatory response. Notably, these immunological markers displayed no direct correlation with S1RBD IgG concentrations, suggesting a complex interaction between the vaccine and the immune system in pregnant women.
CONCLUSIONS
Our pilot study provides valuable insights into the nuanced effects of the mRNA COVID-19 vaccine on immune dynamics in pregnant women, particularly emphasizing the role of microRNAs. The findings illuminate the intricate interplay between vaccines, microRNAs, and immune responses, enhancing our understanding of these relationships in the context of pregnancy. This research contributes significantly to the growing body of knowledge regarding mRNA COVID-19 vaccines and their specific impact on maternal immunology, offering a foundation for further studies in this vital area.
PubMed: 38932387
DOI: 10.3390/vaccines12060658 -
Viruses May 2024The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant...
The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. The clinical characteristics of COVID-19 patients have revealed the possibility of immune activity changes contributing to disease severity. Nevertheless, limited information is available regarding the immune response in human lung tissue, which is the primary site of infection. In this study, we conducted an extensive analysis of lung tissue to screen for differentially expressed miRNAs and mRNAs in five individuals who died due to COVID-19 and underwent a rapid autopsy, as well as seven control individuals who died of other causes unrelated to COVID-19. To analyze the host response gene expression, miRNA microarray and Nanostring's nCounter XT gene expression assay were performed. Our study identified 37 downregulated and 77 upregulated miRNAs in COVID-19 lung biopsy samples compared to the controls. A total of 653 mRNA transcripts were differentially expressed between the two sample types, with most transcripts (472) being downregulated in COVID-19-positive specimens. Hierarchical and PCA K-means clustering analysis showed distinct clustering between COVID-19 and control samples. Enrichment and network analyses revealed differentially expressed genes important for innate immunity and inflammatory response in COVID-19 lung biopsies. The interferon-signaling pathway was highly upregulated in COVID-19 specimens while genes involved in interleukin-17 signaling were downregulated. These findings shed light on the mechanisms of host cellular responses to COVID-19 infection in lung tissues and could help identify new targets for the prevention and treatment of COVID-19 infection.
Topics: Humans; COVID-19; Lung; Gene Regulatory Networks; MicroRNAs; Autopsy; SARS-CoV-2; Male; Female; Middle Aged; Aged; Gene Expression Profiling; RNA, Messenger; Adult
PubMed: 38932146
DOI: 10.3390/v16060853 -
Molecules (Basel, Switzerland) Jun 2024(1) Background: GHaK is derived from the antimicrobial peptide temporin-GHa by substituting the amino acid H with K to enhance its bactericidal activity. The present...
(1) Background: GHaK is derived from the antimicrobial peptide temporin-GHa by substituting the amino acid H with K to enhance its bactericidal activity. The present research aims to broaden the pharmacological potential of GHaK by exploring its antineoplastic activity against human lung adenocarcinoma. (2) Methods: The cell viability, migration, invasion, apoptosis, and cell cycle of A549 and PC-9 cells were tested after GHaK treatment. miRNA sequencing, RT-PCR, Western blotting, and luciferase reporter gene assay were further performed to reveal the potential mechanism. (3) Results: GHaK significantly suppressed cell viability, migration, and invasion; induced apoptosis; and caused cell cycle arrest in the G2/M and S phase in PC-9 and A549 cells, respectively. The miRNA sequencing results show a total of 161 up-regulated and 115 down-regulated miRNAs. Furthermore, the study identified six up-regulated miRNAs (miR-4516, miR-4284, miR-204-5p, miR-12136, miR-4463, and miR-1296-3p) and their inhibitory effects on the expressions of target genes (Wnt 8B, FZD2, DVL3, and FOSL1) caused by miR-4516 directly interacting with Wnt 8B. Western blotting revealed the down-regulation of p-GSK-3β, along with a decreased expressions of cyclin A1 and CDK2 in A549 cells and cyclin B1 and CDK1 in PC-9 cells. (4) Conclusions: Temporin-GHaK exhibits antineoplastic activity against human lung adenocarcinoma by inhibiting the Wnt signaling pathway through miRNA-4516.
Topics: Humans; MicroRNAs; Wnt Signaling Pathway; Adenocarcinoma of Lung; Antineoplastic Agents; Lung Neoplasms; Gene Expression Regulation, Neoplastic; Apoptosis; Cell Line, Tumor; Cell Movement; A549 Cells; Cell Proliferation; Cell Survival; Antimicrobial Cationic Peptides
PubMed: 38930863
DOI: 10.3390/molecules29122797 -
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