Specific miRNAs Research Articles

Understanding microRNAs in the context of bacterial versus viral infections

Introduction. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, have emerged as biomarkers for differentiating infection types due to their distinct expression profiles in response to pathogens. This study explores miRNA profiling using microarray technology to identify miRNA signatures that differentiate viral from bacterial infections in plasma samples. Methods. Plasma samples were collected from patients diagnosed with either bacterial (e.g., pneumonia) or viral (e.g., human papillomavirus) infections; control samples were used to evaluate altered miRNA pattern, followed by Ingenuity Pathway Analysis (IPA) analysis. Results. Microarray analysis revealed distinct miRNA expression patterns for bacterial and viral infections. In bacterial infections, 11 miRNAs were significantly downregulated compared to controls. Similarly, 12 miRNAs were downregulated in viral infections. Pathway analysis indicated that the altered miRNAs in bacterial infections were linked to immune and inflammatory pathways. In contrast, viral infections were associated with miRNAs involved in cellular stress and replication processes. Conclusion. Plasma miRNA profiling offers a promising diagnostic tool to differentiate bacterial from viral infections, providing specific miRNA signatures underlying immune responses. These findings represent a foundation for developing miRNA-based diagnostics, improving the precision of infection diagnosis, and paving the way for targeted therapeutic interventions.

Therapeutic Potential of MSC-Derived Extracellular Vesicles Carrying miRNAs for Modulating Autophagy and Cellular Degeneration in Intervertebral Disc Degeneration.

This research utilized bioinformatics and in vitro modeling to assess the effects of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) containing specific microRNAs (miRNAs) on the autophagy and degeneration of nucleus pulposus (NP) cells in intervertebral disc degeneration (IDD). To determine the therapeutic potential of MSC-EVs loaded with miRNAs in modulating pathological changes in IDD. IDD is characterized by changes in gene expression that contribute to cell degeneration and reduced disc integrity. MSC-EVs are known for their role in cellular communication and potentially reversing these degenerative processes. Key differentially expressed miRNAs and mRNAs in MSC-EVs were identified using bioinformatics analysis. Three miRNAs (miR-486-5p, miR-3648, miR-1827) typically down-regulated in IDD were selected for further study. The bone marrow-derived MSC-EVs used in this study were cultured in a 2D environment. These MSC-EVs were isolated with the purpose of delivering the selected miRNAs to IDD NP cells in vitro, targeting specifically the upregulated genes (SMAD2, ESR1, MAVS, MMP14) associated with autophagy and degeneration. MSC-EV treatment led to significant downregulation of target genes, enhanced cellular proliferation, and decreased apoptosis and autophagy. Overexpression of these target genes produced the opposite effects, confirming the miRNAs' regulatory roles. MSC-EVs carrying specific miRNAs can effectively modulate gene expression, reduce degenerative processes, and promote cellular proliferation in IDD, indicating a promising therapeutic strategy for treating IDD and potentially other degenerative diseases. Further investigations are warranted to explore MSC-EV applications in regenerative medicine.

Screening Model for Bladder Cancer Early Detection With Serum miRNAs Based on Machine Learning: A Mixed-Cohort Study Based on 16,189 Participants.

Early detection of bladder cancer (BCa) can have a positive impact on patients' prognosis. However, there is currently no widely accepted method for early screening of BCa. We aimed to develop an efficient, clinically applicable, and noninvasive method for the early screening of BCa by detecting specific serum miRNA levels. A mixed-cohort (including BCa, 12 different other cancers, benign disease patients, and health population) study was conducted using a sample size of 16,189. Five machine learning algorithms were utilized to develop screening models for BCa using the training dataset. The performance of the model was evaluated using receiver operating characteristic curve and decision curve analysis on the testing dataset, and subsequently, the model with the best predictive power was selected. Furthermore, the selected model's screening performance was evaluated using both the validation set and external set. The BCaS3miR model, utilizing only three serum miRNAs (miR-6087, miR-1343-3p, and miR-5100) and based on the KNN algorithm, is the superior screening model chosen for BCa. BCaS3miR consistently performed well in both the testing, validation, and external sets, exceeding 90% sensitivity and specificity levels. The area under the curve was 0.990 (95% CI: 0.984-0.991), 0.964 (95% CI: 0.936-0.984), and 0.917 (95% CI: 0.836-0.953) in the testing, validation, and external set. The subgroup analysis revealed that the BCaS3miR model demonstrated outstanding screening accuracy in various clinical subgroups of BCa. In addition, we developed a BCa screening scoring model (BCaSS) based on the levels of miR-1343-3p/miR-6087 and miR-5100/miR-6087. The screening effect of BCaSS is investigated and the findings indicate that it has predictability and distinct advantages. Using a mixed cohort with the largest known sample size to date, we have developed effective screening models for BCa, namely BCaS3miR and BCaSS. The models demonstrated remarkable screening accuracy, indicating potential for the early detection of BCa.

Impact of microRNAs on cardiovascular diseases and aging.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality for both men and women among all ethnicities worldwide. Although significant improvements in the management of CVD occurred in the 20th century, non-invasive, universal, early diagnostic biomarkers and newer therapeutic drugs are needed for clinical treatment by physicians. MicroRNAs (miRNAs) are a class of endogenous, non-coding, single-stranded, small RNA molecules that are critically controlled by all human biological processes. Moreover, dysregulated miRNA expression is directly involved in various CVDs, including stable coronary artery disease and acute coronary syndrome. Several miRNAs that are enriched in the plasma of CVD patients have potential as clinical biomarkers, and overexpression or inhibition of specific miRNAs has novel therapeutic significance in the management of CVD. Aging is a multifactorial physiological process that gradually deteriorates tissue and organ function and is considered a non-modifiable major risk factor for CVDs. Recently, several studies established that various miRNAs essentially regulate aging and aging-related disease processes. This narrative review briefly discusses the recently updated molecular involvement of miRNAs in CVDs, their possible diagnostic, prognostic, and therapeutic value, and their relationship to the aging process.

Circulating MicroRNA as a Potential Biomarker for Skeletal Disease in Primary Hyperparathyroidism: A Case-control Study.

The goal of this study was to characterize the microRNA (miRNA) expression signatures in patients with Primary hyperparathyroidism (PHPT) and identify miRNA biomarkers of bone homeostasis. PHPT is associated with increased bone turnover and decreased bone mass. miRNA are markers of bone remodeling. We performed a prospective case-control study of postmenopausal females with PHPT and control subjects matched for race, age, and bone mineral density (BMD). We collected clinical and biochemical data, assessed BMD by dual-energy x-ray absorptiometry, and measured 27 serum miRNAs related to bone remodeling. We used linear regression to assess the correlation between miRNA levels, conventional biochemical markers, and BMD. A total of 135 subjects were evaluated, including 49 with PHPT (discovery group), 47 control patients without PHPT, and an independent validation cohort of 39 PHPT patients. Of 27 miRNAs evaluated, 9 (miR-335-5p, miR-130b-3p, miR-125b-5p, miR-23a-3p, miR-152-3p, miR-582-5p, miR-144-5p, miR-320a, and miR-19b-3p) were differentially expressed in PHPT compared with matched control subjects. All 9 differentially expressed miRNAs significantly correlated with levels of serum parathyroid hormone (PTH), and 8 of the 9 correlated with calcium levels. No differentially expressed miRNAs were consistently correlated with markers of BMD. Subjects with PHPT segregate from controls based on the signature of these 9 miRNAs on principle component analysis. These data suggest that PHPT is characterized by a unique miRNA signature that is distinct from postmenopausal and idiopathic osteoporosis. Levels of specific miRNAs significantly correlate with PTH, suggesting that bone remodeling in PHPT may be mediated in part by PTH-induced changes in miRNA.

MiR-140-3p Improves Sensitivity to Docetaxel by Suppressing PD-L1/ABCG2/MVP Expression in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC) accounts for the majority of non-small cell lung cancer (NSCLC), and overexpression of programmed death ligand 1 (PD-L1) in these cells is known to induce tumor immune evasion or drug resistance. However, detailed studies are needed to determine whether microRNAs (miRNAs) that reduce PD-L1 expression can suppress drug resistance in NSCLC. Kaplan Meier plotter and Receiver Operating Characteristic plotter were used to determine the effect of specific miRNAs on survival and chemotherapy response in NSCLC patients. Cell viability, colony formation and invasion assays, and qPCR analyses were also performed. The expression of miRNA-140-3p (miR-140-3p) was lower in LUAD patients, compared to the normal group, and low expression of miR-140-3p was associated with poor survival of LUAD patients, but not in LUSC. The miR-140-3p mimic inhibited proliferation, colony formation, and invasion of LUAD cells. Interestingly, the expression of miR-140-3p was significantly lower in the group of LUAD patients who did not respond to docetaxel. In LUAD cells, combined treatment with miR-140-3p and docetaxel significantly reduced cell viability as well as the expression of ABCG2 and MVP, genes associated with drug resistance, compared to either treatment alone. Additionally, combined injection of miR-140-3p mimic and docetaxel significantly inhibited tumor growth compared to treatment with docetaxel alone. These results suggest that the high expression of miR-140-3p in LUAD is correlated with good patient prognosis and may contribute to the treatment of LUAD, especially by increasing responsiveness to docetaxel.

Identification of Specific Plasma miRNAs as Potential Biomarkers for Major Depressive Disorder.

Depression is a significant concern in clinical and preclinical psychoneurobiological sciences due to its high prevalence and its individual and collective consequences. Identifying efficient biomarkers for accurate diagnosis is crucial, with ideal biomarkers having detectable serum levels and conformational and thermal stability. This study aims to identify stable plasma biomarkers for the diagnosis and prognosis of major depressive disorder, as the pathogenesis of the disorder remains incompletely understood, affecting diagnosis accuracy. Thus, this study included ten MDD patients and eight healthy controls. The present work analyzed miRNAs in patients with major depressive disorder compared to healthy controls. Eleven specific miRNAs, particularly hsa-miR-874-3p; hsa-let-7d-5p; and hsa-miR-93-3p showed upregulation-type plasma variations in the group of patients with major depressive disorder. miRNA functionality is linked to depressive pathophysiology. This study identifies a "bouquet" of miRNAs with significant upregulation variations in patients with major depressive disorder, suggesting further research to determine their suitability for personalization and evaluation, ultimately becoming integral components of major depression serological evaluations.

Deciphering miRNA signatures in axial spondyloarthritis: The link between miRNA-1-3p and pro-inflammatory cytokines

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that affects the spine and sacroiliac joints. Early detection of axSpA is crucial to slow disease progression and maintain remission or low disease activity. However, current biomarkers are insufficient for diagnosing axSpA or distinguishing between its radiographic (r-axSpA) and non-radiographic (nr-axSpA) subsets. To address this, we conducted a study using miRNA profiling with massive parallel sequencing (MPS) and SmartChip qRT-PCR validation. The goal was to identify differentially expressed miRNAs in axSpA patients, specifically those subdiagnosed with nr-axSpA or r-axSpA. Disease activity was measured using C-reactive protein (CRP) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Radiographic assessments of the cervical and lumbar spine were performed at baseline and after two years. Out of the initial 432 miRNAs, 90 met the selection criteria, and 45 were validated out of which miR-1-3p was upregulated, whereas miR-1248 and miR-1246 were downregulated in axSpA patients. The expression of miR-1-3p correlated with interleukin (IL)-17 and tumour necrosis factor (TNF) levels, indicating its significant role in axSpA pathogenesis. Although specific miRNAs distinguishing disease subtypes or correlating with disease activity or spinal changes were not found, the study identified three dysregulated miRNAs in axSpA patients, with miR-1-3p linked to IL-17 and TNF, underscoring its pathogenetic significance. These findings could help improve the early detection and treatment of axSpA.

Epigenetic Landscapes of Endometriosis: From Pathogenesis to Precision Medicine

Endometriosis, a challenging gynecological disorder characterized by the ectopic presence of endometrial-like tissue, presents significant diagnostic and therapeutic hurdles due to its complex etiology and diverse clinical manifestations. Recent advancements in understanding its pathogenesis have underscored the pivotal role of epigenetic alterations, offering new insights into disease mechanisms and therapeutic targets. Epigenetic changes in endometrial cells significantly contribute to endometriosis pathogenesis, disrupting normal physiology and hormone responsiveness, particularly to progesterone. Dysregulation of histone modifications, DNA methylation, and non-coding RNA expression disrupts cellular homeostasis and promotes disease progression. Histone modifications, notably methylation and acetylation, influence chromatin structure and gene expression, affecting progesterone responsiveness and disease progression. Epigenetic regulators such as Cfp1 modulate progesterone receptor expression and downstream signalling pathways, presenting potential therapeutic targets. Non-coding RNAs, including miRNAs and lncRNAs, exert regulatory effects on gene expression and are implicated in endometriosis pathogenesis. Dysregulated expression disrupts cellular homeostasis and promotes disease progression. Biomarker studies have identified specific miRNAs and lncRNAs associated with endometriosis, offering avenues for non-invasive diagnosis and targeted therapies. siRNA-based therapies targeting key genes involved in endometriosis pathogenesis show promise as novel treatment modalities. By modulating gene expression and cellular functions, siRNA-based therapies offer a targeted approach to mitigate pathological processes. In this review, we summarize recent findings in the molecular mechanisms and regulatory pathways of endometriosis, offering valuable insights into pathology and therapeutic interventions. Future research efforts aimed at elucidating the complex interplay between epigenetic regulators and disease pathways hold promise for innovative diagnostic tools and targeted therapies.

Sheep (Ovis aries) Milk Exosomal miRNAs Attenuate Dextran Sulfate Sodium-Induced Colitis in Mice via TLR4 and TRAF-1 Inhibition.

Mammalian milk exosomal miRNAs play an important role in maintaining intestinal immune homeostasis and protecting epithelial barrier function, but the specific miRNAs and whether miRNA-mediated mechanisms are responsible for these benefits remain a matter of investigation. This study isolated sheep milk-derived exosomes (sheep MDEs), identifying the enriched miRNAs in sheep MDEs, oar-miR-148a, and oar-let-7b as key components targeting TLR4 and TRAF1, which was validated by a dual-luciferase reporter assay. In dextran sulfate sodium-induced colitis mice, administration of sheep MDEs alleviated colitis symptoms, reduced colonic inflammation, and systemic oxidative stress, as well as significantly increased colonic oar-miR-148a and oar-let-7b while reducing toll-like receptor 4 (TLR4) and TNF-receptor-associated factor 1 (TRAF1) level. Further characterization in TNF-α-challenged Caco-2 cells showed that overexpression of these miRNAs suppressed the TLR4/TRAF1-IκBα-p65 pathway and reduced IL-6 and IL-12 production. These findings indicate that sheep MDEs exert gastrointestinal anti-inflammatory effects through the miRNA-mediated modulation of TLR4 and TRAF1, highlighting their potential in managing colitis.

Transcriptome-Wide Evaluation Characterization of microRNAs and Assessment of Their Functional Roles as Regulators of Diapause in Ostrinia furnacalis Larvae (Lepidoptera: Crambidae).

microRNAs (miRNAs) function as vital regulators of diapause in insects through their ability to post-transcriptionally suppress target gene expression. In this study, the miRNA of Ostrinia furnacalis, an economically important global crop pest species, was characterized. For the included analyses, 9 small RNA libraries were constructed using O. furnacalis larvae in different diapause states (non-diapause, ND; diapause, D; diapause-termination, DT). The results identified 583 total miRNAs, of which 256 had previously been identified, whereas 327 were novel. Furthermore, comparison analysis revealed that 119 and 27 miRNAs were differentially expressed in the D vs. ND and DT vs. D, respectively. Moreover, the expression patterns of their miRNAs were also analyzed. GO and KEGG analysis of the target genes of differentially expressed miRNAs highlighted the importance of these miRNAs as diapause regulators in O. furnacalis, especially through metabolic processes, endocrine processes, 20-hydroxyecdysone, and circadian clock signaling pathways. In summary, this study highlighted the involvement of specific miRNAs in the control of diapause in O. furnacalis. To the best of our knowledge, this is the first study to identify miRNA expression patterns in O. furnacalis, thereby providing reference and novel evidence enhancing our current understanding of how small RNAs influence insect diapause.

Major considerations on the relationship of triple negative breast cancer with microRNAs and nutrological triggers: a systematic review

Introduction: Triple-negative breast cancer (TNBC) accounts for 15% of all cases. Its incidence is usually higher in young women (under 40 years of age). The classification as triple-negative occurs because, in this case, there are no estrogen, progesterone, and HER2 receptors, which are responsible for controlling tumor growth. Higher levels of physical activity and better diet quality are associated with lower mortality from breast cancer in observational studies. Furthermore, physical activity and optimal nutrition can improve the relative dose intensity of chemotherapy, as they can activate miRNAs that regulate several biological processes. Objective: This was to conduct a systematic review to establish the main considerations of the relationship between triple-negative breast cancer and microRNAs as biomarkers and regulators of gene expression in cancer cells, as well as to show some nutritional triggers of microRNA activation desirable for breast cancer control. Methods: The PRISMA Platform systematic review rules were followed. The search was conducted from April to June 2024 in the Web of Science, Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE and AMSTAR-2 instrument and the risk of bias was analyzed appropriately. According to the Cochrane instrument. Results and Conclusion: 112 articles were found, and 40 were evaluated in full and included in this article, 22 of which were included in the systematic review. Considering the Cochrane tool for risk of bias, the global assessment resulted in 15 studies with a high risk of bias and 25 studies that did not reach GRADE and AMSTAR-2. Most studies showed homogeneity in their results, with X2=81.5%>50%. It was concluded that an increasing number of studies have shown that non-coding RNA (ncRNA), including microRNA (miRNA) and long non-coding RNA (lncRNA), play a significant role in tumorigenesis. Although a diet and exercise intervention did not affect relative dose intensity, the intervention was associated with a higher pCR in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative and triple-negative breast cancer undergoing neoadjuvant chemotherapy. High expression levels of miR-27a/b, miR-210, and miR-454 were associated with shorter overall survival, whereas high expression levels of miR-454 and miR-374a/b were associated with disease-free survival. The miRNAs associated with triple-negative breast cancer may provide new avenues for early diagnosis and treatment of breast cancer. Furthermore, specific miRNAs may serve as potential prognostic biomarkers in triple-negative breast cancer.

Altered microRNA composition in the uterine lumen fluid in cattle (Bos taurus) pregnancies initiated by artificial insemination or transfer of an in vitro produced embryo

BackgroundMicroRNAs (miRNAs) are presented in the uterine lumen of many mammals, and in vitro experiments have determined that several miRNAs are important for the regulation of endometrial and trophoblast functions. Our aim was to identify and contrast the miRNAs present in extracellular vesicles (EVs) in the uterine lumen fluid (ULF) at the onset of attachment in cattle pregnancies (gestation d 18) initiated by artificial insemination (AI) or by the transfer of an in vitro-produced blastocyst (IVP-ET). A third group had no conceptus after the transfer of an IVP embryo.ResultsThe abundance of 263 annotated miRNAs was quantified in the EVs collected from ULF. There was an increase in the transcript abundance of 20 miRNAs in the ULF EVs from the AI pregnant group, while 4 miRNAs had a lower abundance relative to the group not containing a conceptus. Additionally, 4 miRNAs were more abundant in ULF EVs in the AI pregnant group relative to IVP-ET group (bta-mir-17, bta-mir-7-3, MIR7-1, MIR18A). Specific miRNAs in the ULF EVs were co-expressed with messenger RNAs expressed in extra-embryonic tissues and endometrium, including genes that are known to be their targets.ConclusionsThe results provide biological insights into the participation of miRNAs in the regulation of trophoblast proliferation and differentiation, as well as in endometrium receptivity. The knowledge that in vitro cultured embryos can contribute to the altered abundance of specific miRNAs in the uterine lumen can lead to the development of corrective approaches to reduce conceptus losses during the first month of pregnancy in cattle.

MiRNA expression affects survival in patients with obstructive sleep apnea and metastatic colorectal cancer

IntroductionThe relationship between obstructive sleep apnea (OSA) and cancer has been recognized for some time now. However, little is known about the mechanisms by which sleep apnea promotes tumorigenesis and the impact of OSA on survival after cancer diagnosis. In the last few years, research has focused on the exploration of different biomarkers to understand the mechanisms underlying this relationship and miRNAs, non-coding single strands of about 22 nucleotides that post-transcriptionally regulate gene expression, have emerged as possible actors of this process.The aim of the study was to evaluate the impact of OSA on survival of metastatic colorectal cancer (mCRC) patients based on the expression of specific miRNAs. MethodsThe expression of 6 miRNAs, respectively miR-21, miR-23b, miR-26a, miR-27b, miR-145 and miR-210, was analyzed by qRT-PCR in patients’ sera. Response to first-line therapy, Kaplan-Meier curves of overall and progression-free survival were used to evaluate survival in mCRC patients with and without OSA stratified for the expression of miRNAs. ResultsThe expression of miR-21, miR-23b, miR-26a and miR-210 was significantly upregulated in mCRCs with OSA compared to no OSA. In mCRC patients with OSA and increasing expression of miR-21, miR-23b, miR-26a and miR-210 risk of progression after first-line therapy was higher and both overall and progression-free survival were significantly worst. Conversely, as miR-27b and miR-145 expression increased, the life expectancy of patients diagnosed with OSA and mCRC improved markedly. ConclusionsThis study highlights the relevance of specific miRNAs on OSA in mCRCs and their significance as non-invasive biomarkers in predicting the prognosis in patients with mCRC and OSA.

Blood-based microRNAs as Potential Diagnostic Biomarkers for Melanoma: A Meta-Analysis.

Circulating microRNAs (miRNAs) serve as noninvasive diagnostic markers in many cancers. This meta-analysis aims to evaluate the diagnostic efficacy of circulating microRNAs for melanoma. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and ROC curve were evaluated using the Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.3.3 software packages. To investigate the heterogeneity, the I2 and Chi-square tests were used. The publishing bias was evaluated using Begg's rank correlation and Egger regression asymmetry tests. A total of 9 articles covering 13 studies (more than 50 miRs individually and in combination) were included, containing 1,355 participants (878 cases and 477 controls). The overall pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and AUC were 0.78 (95% CI: 0.76-0.81), 0.80 (95% CI: 0.77-0.83), 4.32 (95% CI: 3.21-5.82), 0.17 (95% CI: 0.09-0.32), 28.0 (95% CI: 15.34-51.09), and 0.91, respectively. According to Begg's and Egger's tests, there was no publication bias (Begg's p = 0.160 and Egger's p = 0.289). Circulating miRNAs can serve as fair and non-invasive diagnostic biomarkers for melanoma. Additionally, specific miRNAs still need to be discovered for diagnosing melanoma.

Exploring the role of FAT genes in Solanaceae species through genome-wide analysis and genome editing.

Plants produce numerous fatty acid derivatives, and some of these compounds have significant regulatory functions, such as governing effector-induced resistance, systemic resistance, and other defense pathways. This study systematically identified and characterized eight FAT genes (Acyl-acyl carrier protein thioesterases), four in the Solanum lycopersicum and four in the Solanum tuberosum genome. Phylogenetic analysis classified these genes into four distinct groups, exhibiting conserved domain structures across different plant species. Promoter analysis revealed various cis-acting elements, most of which are associated with stress responsiveness and growth and development. Micro-RNA (miRNA) analysis identified specific miRNAs, notably miRNA166, targeting different FAT genes in both species. Utilizing clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated knockout, mutant lines for SlFATB1 and SlFATB3 were successfully generated and exhibited diverse mutation types. Biochemical evaluation of selected mutant lines revealed significant changes in fatty acid composition, with linoleic and linolenic acid content variations. The study also explored the impact of FAT gene knockout on tomato leaf architecture through scanning electron microscopy, providing insights into potential morphological alterations. Knocking out of FAT genes resulted in a significant reduction in both trichome and stoma density. These findings contribute to a comprehensive understanding of FAT genes in Solanaceous species, encompassing genetic, functional, and phenotypic aspects.

MicroRNAs: pioneering regulators in Alzheimer’s disease pathogenesis, diagnosis, and therapy

This article delves into Alzheimer’s disease (AD), a prevalent neurodegenerative condition primarily affecting the elderly. It is characterized by progressive memory and cognitive impairments, severely disrupting daily life. Recent research highlights the potential involvement of microRNAs in the pathogenesis of AD. MicroRNAs (MiRNAs), short non-coding RNAs comprising 20–24 nucleotides, significantly influence gene regulation by hindering translation or promoting degradation of target genes. This review explores the role of specific miRNAs in AD progression, focusing on their impact on β-amyloid (Aβ) peptide accumulation, intracellular aggregation of hyperphosphorylated tau proteins, mitochondrial dysfunction, neuroinflammation, oxidative stress, and the expression of the APOE4 gene. Our insights contribute to understanding AD’s pathology, offering new avenues for identifying diagnostic markers and developing novel therapeutic targets.

Muscle Atrophy and mRNA-miRNA Network Analysis of Vascular Endothelial Growth Factor (VEGF) in a Mouse Model of Denervation-Induced Disuse.

Skeletal muscle atrophy is frequently caused by the disuse of muscles.It impacts quality of life, especially in aging populations and those with chronic diseases. Understanding the molecular mechanisms underlying muscle atrophy is crucial for developing effective therapies. To investigate the roles of vascular endothelial growth factor (VEGF) and various microRNAs (miRNAs) in muscle atrophy using a mouse model of denervation (DEN)-induced disuse, and to elucidate their interactions and regulatory functions through comprehensive network analysis. The right sciatic nerve of C57BL/6J mice (n=6) was excised to simulate DEN, with the left serving as a sham surgery control (Sham). Following a two-week period, wet muscle weight was measured. Total RNA was extracted from the tibialis anterior muscle for microarray analysis. Significant expression changes were analyzed via Kyoto Encyclopedia of Genes and Genomes (KEGG)pathway analysis and miRNet for miRNAs. Denervated limbs showed a significant reduction in muscle weight. Over 1,000 genes displayed increased expression, while 527 showed reductions to less than half of control levels. VEGF, along with specific miRNAs such as miR-106a-5p, miR-mir20a-5p, mir93-5p and mir17-5p, occupied central regulatory nodes within the gene network. Functional analysis revealed that these molecules are involved in key biological processes including regulation of cell migration, vasculature development, and regulation of endothelial cell proliferation. The increased miRNAswere subjected to further network analysis that revealed significant regulatory interactions with target mRNAs. VEGF and miRNAs play crucial roles in the progression of skeletal muscle atrophy, offering potential targets for therapeutic interventions aimed at reducing atrophy and enhancing muscle regeneration.

Evaluating the Serum Level of ACTH and Investigating the Expression of miR-26a, miR-34a, miR-155-5p, and miR-146a in the Peripheral Blood Cells of Multiple Sclerosis Patients.

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disorder affecting white and gray matter. This study aimed to investigate the association between clinical outcomes in MS patients and the levels of certain molecules in their serum, including ACTH, IL-17, and specific miRNAs: miR-26a, miR-34a, miR-155-5p, and miR-146a. Fifty healthy people and 75 blood samples from MS patients were selected. MS patients had higher expression levels of IL-17, miR-26a, miR-34a, and miR-146a compared to healthy individuals (p < 0.0001). There was no significant difference in miR-155-5p expression between the two groups (p = 0.203). MS patients also had higher serum levels of ACTH compared to the normal population (p < 0.0001). In MS patients, there was a negative correlation between IL-17 and miR-155-5p expression levels (p = 0.048, r = - 0.229). Similarly, a significant negative correlation was observed between ACTH and miR-155-5p in the control group (p = 0.044, r = - 0.286). The study's analysis revealed no significant difference in the expression of miR-155-5p between MS patients and normal individuals; the study's examination revealed that the expression level of IL-17, miR-26a, miR-34a, and miR-146a was higher in MS patients than in normal individuals.

Abstract P360: MicroRNAs: Potential Biomarkers and Therapeutic Targets for Hypertensive Nephropathy

Introduction: Hypertensive nephropathy (HN) is the second most common cause of end-stage renal disease after diabetic nephropathy. miRNAs are small epigenetic modulators whose levels change in many diseases. This review summarizes the diagnostic and therapeutic potential of miRNAs in HN. Methodology: We conducted a thorough literature review on PubMed, including both retrospective and prospective studies on animal and human subjects. Additional references were sourced through cross-referencing the bibliographies of the initial articles. Results: Our literature review revealed that intra-renal levels of miR-200a, miR-141, miR-200b, miR-205, miR-429, and miR-192 were elevated in patients with HN. Conversely, intra-renal miR-204-5p levels were decreased, and further reductions in animal models using anti-miR-204-5p or miR-204 gene knockout exacerbated renal injury. Exposure of renal tissue to exogenous albumin increased intra-renal miR-184 levels, prompting further investigation into whether albumin excretion from kidney injury alters miRNA expression or if miRNA dysregulation initiates kidney injury and subsequent albumin excretion. Urinary miR-146a, miR-184, and miR-34a levels were lower in patients with albuminuria than those without, whereas urinary miR-200a levels were higher. Interestingly, urinary miR-21 levels increased before the onset of albuminuria in hypertensive mice. A positive correlation was also observed between miR-208b and miR-133a levels in blood cells and urinary albumin excretion (UAE). Notably, plasma levels of miR-let-7g-5p and miR-191-5p correlated positively with eGFR but not with UAE. Since miRNA levels varied based on the sampling source, a pivotal study identified a consistent miRNA profile in HN patients, showing that miR-208a and miR-301a were upregulated in urine yet downregulated in plasma. The therapeutic potential of miRNAs was highlighted by an animal study showing that the knockdown of miR-103a-3p can nullify albuminuria in hypertensive mice. Conclusion: The role of miRNAs in HN is increasingly evident. Studies have linked varying miRNA expression profiles in patients with HN, and specific miRNAs were detectable earlier than albuminuria. Furthermore, certain miRNAs correlate with eGFR independently of UAE. Targeting specific miRNAs, using miRNA mimics and anti-miRNAs, could underpin preventive and therapeutic strategies. These findings advocate for further research into miRNAs as potential biomarkers and therapeutic targets for HN.