Search Results (824)

Background: Ulcerative colitis (UC), a chronic and relapsing form of inflammatory bowel disease (IBD), arises from a multifactorial interplay of genetic predisposition, immune dysregulation, and environmental triggers. Despite advances in understanding UC pathogenesis, the identification of reliable biomarkers and key regulatory genes remains essential for unraveling disease mechanisms. Such insights are crucial for improving diagnostic precision and developing personalized therapeutic strategies. Methods: In this study, gene expression profiles from publicly available microarray and RNA-sequencing datasets were systematically analyzed using advanced bioinformatics tools. Differentially expressed genes (DEGs) were identified through statistical comparisons, and functional enrichment analyses were performed to explore their biological relevance. A total of 141 overlapping DEGs were extracted from three GEO datasets, and 20 key DEGs were further prioritized via protein–protein interaction (PPI) network construction. Hub genes, relevant signaling pathways, associated transcription factors (TFs), and microRNAs (miRNAs) linked to disease progression were identified. Potential therapeutic compounds were also predicted through computational drug–gene interaction analysis. Results: The analysis revealed a panel of novel biomarkers-TLR2, IFNG, CD163, CXCL9, CCL4, PRF1, TLR8, ARG1, LILRB2, FPR2, and PPARG-that function as key hub genes implicated in ulcerative colitis (UC) pathogenesis. These genes were associated with critical biological processes including signal transduction, inflammatory and immune responses, proteolysis, lipid transport, and cholesterol/triglyceride homeostasis. Furthermore, transcription factors (FOXC1, GABPA, GATA2, SUPT5H) and microRNAs (hsa-miR-34a-5p, hsa-miR-335-5p, hsa-miR-24-3p, hsa-miR-23a-5p, hsa-miR-26a-5p) revealed key regulatory networks influencing post-transcriptional gene regulation. Molecular docking analysis predicted Apremilast and Golotimod as promising therapeutic candidates for UC intervention. Conclusions: In conclusion, this study enhances our understanding of ulcerative colitis pathogenesis by identifying key biomarkers and therapeutic targets, paving the way for future advancements in personalized diagnosis and treatment strategies. Full article

Formaldehyde (FA) is commonly used for hatchery disinfection, where it reduces microbial growth, ensures successful egg hatch and enhances healthy production, but its specific effects on embryonic development remain unclear. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and may mediate FA-induced transcriptional responses. Here, we investigated the impact of FA treatment on miRNA profiles in chicken embryo liver. Small RNA-seq libraries were constructed and sequenced using the Illumina NextSeq platform. Reads were trimmed and quantified using miRDeep2 version 2.0.0.3. Differential expression analysis was performed with DESeq2 (p-adjusted < 0.05 and |log2FC| > 1). Target genes of differentially expressed miRNAs (DEMs) were predicted with miRDB, and GO/KEGG/Reactome enrichment was conducted. Out of 662 total mature miRNAs detected, differential expression analysis identified 30 DEMs (11 up-regulated, 19 down-regulated). The highest fold increase was determined for gga-miR-3533 (log2FC = 4.45), and the most significant decrease was determined for gga-miR-133b (log2FC = −3.38). Pathway analysis revealed miRNAs affecting signaling pathways along with modules related to post-translational protein modification, immune system, and oxidative stress pathways. Our study demonstrates that FA treatment can affect critical biological processes by altering miRNA-mediated regulation in the developing embryonic liver and point to the need for functional validation of miRNA-target interactions to help determine mechanisms for FA benefits. Long term, these data may help serve as reference to identify new treatments with optimized response profiles. Full article

The emergence of single-cell sequencing and computational analysis has dramatically improved our understanding of cellular diversity and gene expression dynamics. The rapid advancement of high-throughput omics technologies has led to an exponential growth in biological data. However, many gene regulatory processes at the single-cell level remain underexplored, especially those regulated by post-transcriptional mechanisms involving microRNAs (miRNAs). miRNAs are essential regulators of gene expression, affecting cellular functions in both normal and disease states. Recent innovations, such as single-cell gene expression profiling and bioinformatic analysis, have enabled comprehensive studies that uncover previously hidden miRNA profiles. In this context, we present experimental tools and computational methods for analysing cell-specific miRNA abundance and investigating their mechanisms. These approaches are expected to reveal the complex nature of miRNA biology and, more broadly, enhance our understanding of life sciences and diseases. Full article

Background/Objectives: Oocyte maturation is a process involving both nuclear and cytoplasmic development regulated by epigenetic changes in gene expression. Cyclin-B3 (CCNB3) and cyclin-A2 (CCNA2) genes are thought to be involved in oocyte maturation; however, the expression profiles and key function in Metaphase-I (MI) and Metaphase-II (MII) phases have yet to be fully elucidated. Small non-coding RNA sequences are involved in epigenetic regulation of specific transcriptional targets, whereas microRNAs (miRNAs) participate in the post-transcriptional and translational repression of target genes. This study examined the expression levels of CCNB3, CCNA2, and their associated miRNAs (miR-17, miR-106b, miR-190a, miR-1275) in cumulus oophorous complex (COC) cells derived from MI and MII oocytes of NOR and DOR IVF cases, with particular emphasis on elucidating their functions during the transition from MI to MII stage. Methods: Follicular fluid containing cumulus–oocyte complex (COC) cells obtained from oocytes of 120 cases in each group NOR MI (n = 30), NOR MII (n = 30), DOR MI (n = 30), and DOR MII (n = 30) who were admitted to the Istanbul Bahçeci Health Group Assisted Reproductive Treatment Center. Following total RNA isolation from COC cells, the gene and protein expression levels of CCNB3 and CCNA2, along with the expression of miR-17, miR-106b, miR-190a, and miR-1275, were assessed using (qPCR-based assay) and immunohistochemistry (IHC). To investigate the functional roles of COC cell populations, morphological analysis was performed using H&E staining. Additionally, metadata of the cases, including age, number of oocytes, fertilization, and embryonic development rates, were evaluated. Results: The expressions of miR-17 and miR-1275 were significantly elevated in both NOR MI and DOR MI groups compared to their respective NOR MII and DOR MII groups (p < 0.05). Additionally, miR-106b levels were higher in the NOR MII group relative to NOR MI (p < 0.05), while an increase was also observed in DOR MI compared to DOR MII (p < 0.05). No difference was observed in miR-190a expression between the NOR and DOR (p > 0.05). Based on the results of H and E staining, the NOR MI, NOR MII, DOR MI, and DOR MII groups exhibited distinct variations in cellular morphology, nuclear characteristics, cytoplasmic volume, and cell density. Conclusions: CCNB3 is predicted to be a potential candidate for determining MI between the NOR and DOR cases. On the other hand, only for the NOR MII cases could CCNA2 provide evidence of oocyte maturation. Moreover, we determined the relationship between related genes and miRNAs which target CCNA2 and CCNB3. Genetic and protein expression analysis across diverse molecular pathways and miRNAs yielded comprehensive preliminary data regarding the developmental stages of oocytes at the MI and MII phases, and their fertilization potential following maturation shows potential and warrants prospective validation with clinical performance evaluation. Full article

Background: The mitogen-activated protein kinase (MAPK) signaling pathway is frequently dysregulated in cutaneous squamous cell carcinoma (cSCC). Tumor progression locus 2 (Tpl2), a serine/threonine protein kinase within the MAPK family, regulates cellular proliferation, survival, and inflammatory responses. Loss of Tpl2 activates compensatory signaling cascades, driving increased papilloma and cSCC development. In this study we examined whether dysregulated ErbB signaling contributes to the enhanced tumor burden found in Tpl2^−/− mice. Methods: To evaluate whether aberrant ErbB signaling drives tumorigenesis in Tpl2^−/− mice, wild-type (Tpl2^+/+) and Tpl2^−/− mice were subjected to a two-stage chemical carcinogenesis protocol for 48 weeks. A subset of mice received Gefitinib (an EGFR inhibitor) or Lapatinib (a HER2 inhibitor) in their diet. Results: We found that Tpl2 ablation increases gene expression of EGFR, HER2, and HER3, while baseline protein levels remain unchanged between Tpl2 genotypes. To investigate the possibility of microRNA (miR)-mediated post-transcriptional regulation of EGFR, HER2, and HER3, we measured ErbB-related miR expression in keratinocytes. We found that HER2/3-related miRs 205 and 21 are increased in Tpl2^−/− keratinocytes. Further, Tpl2 loss enhances p-EGFR, EGFR, and HER2 protein expression in papillomas. and HER2-related microRNAs (miRs) 205 and 21 in keratinocytes, and enhances p-EGFR, EGFR, and HER2 protein expression in papillomas. Tpl2^−/− mice developed 12-fold more papillomas and 4-fold more cSCCs compared to Tpl2^+/+ animals. Treatment with Gefitinib or Lapatinib reduced papilloma numbers by 88% and 50%, respectively, while restoring cSCC numbers to Tpl2^+/+ levels. Conclusions: These findings indicate that ErbB targeting represents a promising therapeutic strategy for cSCCs arising from MAPK pathway dysregulation. Full article

Background: Brown adipose tissue (BAT) is indispensable for producing heat and contributes critically to the survival of neonatal mammals. MicroRNAs (miRNAs) are small noncoding RNAs that serve as key post-transcriptional regulators, playing a crucial role in regulating BAT development and thermogenesis. However, the role of miR-326-3p in goat brown adipocytes remains largely unclear. Methods: Primary brown adipocytes were isolated from goat perirenal adipose tissue and subjected to gain and loss-of-function assays using miR-326-3p mimics and inhibitors. Lipid accumulation, thermogenic-related genes, and mitochondrial gene expression were quantified by Oil Red O staining and qRT-PCR. Target prediction and dual-luciferase reporter assays were performed to validate direct interaction between miR-326-3p and FGF11. Results: Expression profiling demonstrated that miR-326-3p is more enriched in brown adipose tissue (BAT) than in white adipose tissue (WAT), and the expression level gradually decreases with adipocyte differentiation. miR-326-3p overexpression significantly inhibited lipid droplet accumulation and the expression of genes associated with differentiation, thermogenesis, and mitochondria, including PPARγ, FABP4, UCP1, and PGC1α, whereas inhibition produced the opposite effect. Bioinformatic prediction and dual-luciferase reporter assays further identified fibroblast growth factor 11 (FGF11) as a direct target of miR-326-3p. Conclusions: These findings reveal that miR-326-3p negatively regulates the differentiation and expression of thermogenic-related genes of goat brown adipocytes, uncovering a novel miR-326-3p-FGF11 regulatory axis. Full article

MicroRNA (miRNA), as a key post-transcriptional regulatory factor, plays a crucial role in embryonic development. The coordination of endoderm cell convergence and cardiac precursor cell (CPC) migration is critical for cardiac tube fusion. Defects in endoderm can impair the normal migration of CPCs towards the midline, leading to cardia bifida. Although the role of the microRNA-183 family (miR-183, miR-96 and miR-182) in cardiovascular diseases has been reported, the mechanism by which they regulate early heart development remains unclear. In this study, we used zebrafish as a model to elucidate the roles of the microRNA-183 family in early heart development. miRNA mimics were injected into Tg (cmlc2: eGFP) and Tg (sox17: eGFP) transgenic embryos to overexpress the miR-183 family. The results showed that, at 36 hpf, single or co-injection of miR-183/96/182 mimics caused defects in endoderm convergence, with a hole in the endoderm, and a significant down-regulation of the endoderm marker gene sox32. Additionally, embryos with single or co-injection of miR-183/96/182 mimics exhibited cardia bifida and tail blisters, with significantly down-regulated expression levels of genes related to heart development, including cmlc2, vmhc, amhc, nppa, gata4, gata5, nkx2.5, bmp2b, and bmp4. The phenotype caused by overexpression of the miR-183 family is highly consistent with loss of the sphingosine 1-phosphate receptor S1Pr2. Bioinformatics analysis result found that miR-183 can bind to 3′-UTR of the s1pr2 to regulate its expression; overexpression of miR-183 led to a significant decrease in the expression of the s1pr2 gene. Dual luciferase assay results suggest that s1pr2 is a bona fide target of miR-183. In summary, the miR-183 family regulates endoderm convergence and cardiac precursor cell migration via the S1Pr2 signaling pathway. This study reveals that the miR-183 family is a key regulatory factor in endoderm convergence and cardiac precursor cell migration during the early zebrafish development, elucidating the molecular mechanisms underlying early cardiac precursor cell and endoderm cell movement. Full article

The Nile tilapia (Oreochromis niloticus), a key aquaculture species, displays marked sexual growth dimorphism, with males growing faster than females. This process is governed by intricate interactions between antagonistic regulators, including transcription factors, growth factors, and steroid hormones, operating through sex-specific developmental pathways. While circular RNAs (circRNAs) are known to modulate gene expression by sponging microRNAs (miRNAs), their role in teleost sex differentiation remains poorly understood. To address this gap, we profiled circRNA expression in tilapia gonads by constructing six circRNA libraries from testes and ovaries of 180 days after hatching (dah) fish, followed by high-throughput sequencing. We identified 6564 gonadal circRNAs distributed across all 22 linkage groups, including 226 differentially expressed circRNAs (DECs; 108 testis-biased, 118 ovary-biased). Functional enrichment analysis linked their host genes to critical pathways such as cAMP signaling, cell adhesion molecules, and—notably—sexual differentiation processes (e.g., estrogen signaling, oocyte meiosis, and steroid hormone biosynthesis). Furthermore, we deciphered competing endogenous RNA (ceRNA) networks, uncovering circRNA–miRNA–mRNA interactions targeting germ cell determinants, sex-specific transcription factors, and steroidogenic enzymes. This study provides the first systematic exploration of circRNA involvement in tilapia sex differentiation and gonadal differentiation, offering novel insights into the post-transcriptional regulation of sexual dimorphism. Our findings advance the understanding of circRNA biology in fish and establish a framework for future studies on aquaculture species with similar reproductive strategies. Full article

MicroRNAs (miRNAs) are small non-coding RNAs that play pivotal roles in post-transcriptional gene regulation, influencing development, differentiation, and disease pathogenesis. Since their discovery in 1993, miRNAs have been recognized for their evolutionary conservation and pleiotropic effects, with the 2024 Nobel Prize underscoring their significance in post-transcriptional regulation via the RNA interference (RNAi) pathway. This review synthesizes the complete life cycle of miRNAs—from transcription and processing to function and decay—emphasizing regulatory mechanisms and their implications in human diseases, particularly cancer. We discuss how epitranscriptomic modifications influence miRNA biogenesis and activity, explore their nuclear and mitochondrial functions, and address emerging challenges in miRNA-based therapeutics, including the expanding small RNA landscape such as tRNA-derived small RNAs (tsRNAs), and Argonaute (AGO)-independent activities. Despite hurdles such as modest multi-target effects, off-target interactions, and delivery challenges, miRNAs remain promising as both biomarkers and therapeutic agents, underscoring the need for sustained research to bridge preclinical insights with clinical applications. Full article

Postpartum uterine diseases such as metritis and endometritis impair reproductive performance and cause substantial economic losses in dairy cows worldwide. The multifactorial etiology, involving polymicrobial infections and complex host immune responses, poses diagnostic and therapeutic challenges. Traditional treatments rely on antibiotics, e.g., cephalosporins like ceftiofur and cephapirin, with broad-spectrum efficacy. However, emerging antimicrobial resistance, biofilm formation by pathogens such as Trueperella pyogenes, Fusobacterium necrophorum, and Escherichia coli, and bacterial virulence factors have reduced effectiveness of conventional therapies. Advances in systems biology, particularly proteomics, metabolomics, and microRNA (miRNA) profiling, have provided unprecedented insights into the molecular mechanisms underpinning uterine disease pathophysiology. Proteomic analyses reveal dynamic changes in inflammatory proteins and immune pathways, whereas metabolomics highlight shifts in energy metabolism and bacterial–host interactions. Furthermore, miRNAs have critical roles in post-transcriptional gene regulation affecting immune modulation, inflammation, and tissue repair, and also in modulating neutrophil function and inflammatory signaling. Uterine inflammation not only disrupts local tissue homeostasis but also compromises early embryo development by altering endometrial receptivity, cytokine milieu, and oocyte quality. Integration of multi-omics approaches, combined with improved diagnostics and adjunct therapies—including micronutrient supplementation and immunomodulators—offers promising avenues for enhancing disease management and fertility in dairy herds. This review synthesizes current knowledge on proteomics, metabolomics, and miRNAs in postpartum uterine diseases and highlights future directions for research and clinical applications. Full article

Glutamine synthetase plays an essential role in regulating plant growth and development. However, few studies have analyzed the roles of TaGS in wheat under abiotic stress conditions. In this study, we identified and analyzed the members of the TaGS gene family in Triticum aestivum L., focusing on their gene characteristics, phylogenetic evolution, cis-elements, transcriptional and post-translational modifications, and expression profiling in response to abiotic stress. Twelve TaGS genes were divided into four subfamilies. The synteny analysis revealed that wheat and the five other species share GS homologs. Several potential transcription factors were identified as regulators of TaGS genes. TaGS contains 19 microRNA binding sites, phosphorylation sites, and ubiquitination sites. TaGS genes exhibited tissue-specific expression across various developmental stages and were differentially expressed in response to abiotic stress. For instance, TaGS1-3-4A/4B/4D were upregulated in the leaves and roots of wheat seedlings under abiotic stress conditions. Furthermore, gene ontology annotation was performed on the TaGS-interacting proteins screened by immunoprecipitation–mass spectrometry to elucidate the regulatory network associated with TaGS. This study lays a foundation for further functional research of TaGS genes in response to abiotic stress and provides potential information for enhancing stress tolerance in wheat. Full article

Background/Objectives: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG nucleotide repeat expansion in the Huntingtin (HTT) gene. Dysregulation of microRNAs (miRNAs), key post-transcriptional regulators of gene expression, has been implicated in HD pathogenesis, although their specific roles remain incompletely understood. Methods: Peripheral blood mononuclear cells from Sicilian HD patients and matched healthy controls were subjected to small RNA sequencing. Differential expression analysis was conducted using DESeq2 (version 1.44.0), with significance defined as |fold change| ≥ 1.5 and adjusted p ≤ 0.05. Ingenuity Pathway Analysis (IPA) was applied to assess functional enrichment, focusing on neurological diseases, inflammatory processes, and miRNA–RNA messenger (mRNA) interaction networks. Results: A total of 790 differentially expressed miRNAs were identified in HD patients (270 upregulated and 520 downregulated). IPA revealed enrichment in pathways related to organismal injury, neurological disease, and inflammatory responses. Four major regulatory networks linked differentially expressed miRNAs to neurodegenerative processes, with target genes involved in neuroinflammation, cellular stress responses, and metabolic dysfunction. Cross-referencing with previous RNA-seq data identified 5721 high-confidence miRNA–mRNA interactions, implicating 721 target genes across 54 key canonical pathways. Conclusions: HD patients exhibit a distinct and reproducible peripheral blood miRNA expression signature. These dysregulated miRNAs may represent accessible biomarkers and provide mechanistic insights into HD pathogenesis, with potential applications for diagnosis, prognosis, and therapeutic development. Full article

Nuclear receptor subfamily 4 group A member 2 (NR4A2) is a transcription factor that regulates the expression of different genes involved in essential biological processes, including cell proliferation, neuronal development, immune response, cellular stress, apoptosis, DNA repair, and angiogenesis. The gene encoding this transcription factor is called NR4A2 and has been identified as an immediate early gene. Moreover, research in animal models and clinical trials has suggested an association between reduced NR4A2 gene expression and some neurodegenerative diseases and psychiatric disorders. These include Parkinson’s disease, Alzheimer’s disease progression, schizophrenia, substance abuse (alcohol and amphetamines), neurodevelopmental disorders, and cognitive imairment. NR4A2 activity is controlled at multiple levels, including transcriptional and post-transcriptional regulation of its gene expression, such as translational and post-translational processes. This review summarizes the current knowledge of the NR4A2 gene, encompassing its structure and the molecular mechanisms that regulate its expression. The key epigenetic mechanisms that regulate its gene expression are emphasized, including DNA methylation, histone deacetylation, and regulation by microRNAs. It also addresses its role in central nervous system pathologies associated with dysregulation of NR4A2 gene expression. Finally, we discuss the potential of these regulatory mechanisms as biomarkers and therapeutic targets for neurodegenerative diseases and psychiatric disorders. Full article

The growing demand for sustainable alternatives to petroleum-based plastics has driven interest in bio-based packaging derived from renewable plant biomass. Cellulose, the most abundant biopolymer on Earth, provides high tensile strength, water resistance, and biodegradability, making it a key raw material for eco-friendly packaging. However, its extraction and processing are hindered by lignin, a complex polymer that adds structural rigidity but reduces cellulose accessibility. Recent research has identified plant microRNAs (miRNAs) as powerful post-transcriptional regulators capable of modifying cell wall composition by simultaneously targeting multiple genes involved in lignin biosynthesis, cellulose synthesis, and secondary cell wall formation. By fine-tuning specific miRNAs, it is possible to increase cellulose yield, reduce lignin content, and enhance overall biomass productivity without severely compromising plant growth or stress tolerance. This review summarizes the roles of major plant miRNAs in biomass regulation and outlines biotechnological strategies such as transgenic overexpression, target mimicry, artificial miRNAs (amiRNAs), and CRISPR-based editing for improving bio-based packaging feedstocks. Harnessing miRNA-mediated gene regulation offers a promising pathway toward producing high-quality biomass with optimized cellulose–lignin ratios, enabling more efficient, cost-effective, and sustainable packaging material production. Full article

Heart failure with a preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases. It continues to impose a significant global cardiovascular burden due to its rising prevalence, complex pathophysiology, and limited treatment options. The absence of effective disease-modifying therapies is primarily attributable to the complex and heterogeneous pathophysiology underlying HFpEF. The hallmark of HFpEF is systemic inflammation, mostly originating from extracardiac comorbidities, which initiates and sustains the process of myocardial fibrosis, resulting in diastolic dysfunction. Recent evidence has identified specific micro ribonucleic acids (miRNAs) as key regulatory molecules in this inflammation–fibrosis cascade. Particularly, miR-21 and miR-29 play a central role in modulating these pathological processes by regulating the post-transcriptional expression of genes involved in inflammation, cardiac fibrosis, and remodeling. The inflammation-fibrosis axis in HFpEF offers multiple therapeutic opportunities ranging from direct anti-fibrotic strategies to the modulation of inflammation and fibrosis-related miRNA signatures. Such targeted approaches, especially miRNA modulation, hold potential to disrupt fundamental molecular mechanisms driving disease progression, moving beyond conventional HFpEF management. This narrative review explores the roles of miRNAs in modulating inflammation and fibrosis in HFpEF, critically assesses their potential as diagnostic and prognostic biomarkers, and evaluates their therapeutic application. Given the urgent clinical need for efficient HFpEF treatment strategies, understanding miRNA-mediated regulation of the inflammation–fibrosis axis is essential for developing personalized, mechanism-based therapies for HFpEF that could fundamentally change the HFpEF management paradigm. Full article