Search Results (69)

miRNA 183 is part of the miRNA-183/96/182 cluster, which is known to play a decisive role in fine-tuning the activity of gene expression in sensory systems, particularly in the retina. Although miR-183 is essential for retinal gene expression in mammals, the contributions of miR-183 to mRNA expression and photoreceptor development and function in other classes of animals have not been fully elucidated. Danio rerio have a diverse photoreceptor system, with cone photoreceptors sensitive to red, green, blue and ultraviolet (UV) light. We generated knockout zebrafish by deleting the whole seed sequence of miR-183. RNAscope results show no expression of mature miR-183 and decreased expression of miR-182 in both dorsal and ventral KO retinas. The number of UV and blue photoreceptors decreased, and the photoreceptors showed shortening or loss of their outer segments. In the absence of miR-183, the transcription levels of phototransduction genes were altered differentially at 3 and 12 months of age. Finally, photoreceptor-only electroretinogram (PIII) signals showed attenuated amplitudes of red and green-sensitive photoreceptor subtypes while the b-wave amplitudes reflecting second order retinal neuron activity, were decreased in response to the UV-, blue-, and red-stimulating wavelengths. These results reveal a novel microRNA regulatory network in teleost fish and indicate that miR-183 plays a facilitative role in retinal development and function, especially for short-wavelength-sensitive photoreceptor subtypes. Full article

Oncometabolites and hypoxia-regulated exosomes orchestrate hypoxia-inducible factor (HIF)–driven macrophage reprogramming across chronic cardiometabolic and oncologic conditions. In type 2 diabetes (T2D) and obesity, regional hypoxia in expanding white adipose tissue (WAT) reconfigures macrophage immunometabolism and chemokine signaling, recruits C-C chemokine receptor 2 (CCR2⁺) monocytes, and skews adipose-tissue macrophages toward M1-like programs that sustain low-grade inflammation and blunt the physiological M1-to-M2 transition during wound repair. In atherosclerotic plaques, lipid-core hypoxia stabilizes HIF-1α, amplifies nuclear factor kappa-light-chain-enhancer of activated B cells/reactive oxygen species (NF-κB/ROS) signaling, increases matrix metalloproteinase-2/-9 (MMP-2/-9) release, and reduces ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux, weakening the fibrous cap. In tumors, poorly perfused niches accumulate lactate and succinate, which act as paracrine cues. Lactate activates PKA/cAMP pathways and promotes immunosuppressive tumor-associated macrophages (TAMs), whereas succinate signals through succinate receptor 1 (SUCNR1) to reinforce HIF-1α–dependent transcription and M2-like programming. In parallel, hypoxia-regulated exosomes deliver microRNAs such as miR-301a-3p, which suppress phosphatase and tensin homolog (PTEN) and activate PI3Kγ, thereby augmenting immunosuppression and programmed death-ligand 1 (PD-L1) expression. Clinically, this hypoxia–oncometabolite–exosome triad links oxygen debt with macrophage state, plaque destabilization, impaired wound repair, and tumor immune escape. Translational entry points include selective HIF-2α inhibition, phosphoinositide 3-kinase gamma (PI3Kγ) blockade, SUCNR1 targeting, and exosome-based miRNA modulation, while a biomarker panel comprising HIF-1α, vascular endothelial growth factor A (VEGF-A), and MMP-9 offers a pragmatic readout of hypoxia burden, macrophage programming, and therapeutic response. We conducted a focused narrative review (PubMed, Scopus, Web of Science; English; 2003–2025), prioritizing mechanistic and translational studies on hypoxia–HIF, lactate/succinate, and hypoxia-regulated exosomes across T2D, atherosclerosis, and cancer. Full article

Agriculture is still at serious risk from viral infections, particularly in light of climate change and more intensive farming practices. Small non-coding RNAs (sRNAs), in particular microRNAs (miRNAs) and circular RNAs (circRNAs), have emerged as crucial post-transcriptional regulators of plant antiviral defense in this setting. These molecules provide an essential RNA-based immunity layer by regulating hormones, autophagy, redox balance, immunological signaling, and programmed cell death. In this work, we examine the molecular processes through which circRNAs and miRNAs function during viral infection, focusing on how they affect autophagy and systemic acquired resistance (SAR). Through thorough searches of PubMed, Web of Science, and Scopus, we combined findings from peer-reviewed experimental and transcriptomic studies. Our study covers important crops as well as model species (Arabidopsis thaliana, Nicotiana benthamiana), providing a thorough understanding of sRNA synthesis, target control, and antiviral signaling. By combining previously disparate data, this review provides a coherent framework for understanding how short RNAs affect plant immune responses to viral infections. We highlight key regulatory relationships that need further study and propose that these results can be used as a foundation for new RNA-based biotechnological approaches. By carefully altering RNA regulatory mechanisms, scientists can use this information to help them create more resistant crops. Full article

The Kazakh horse is a highly valuable indigenous Chinese breed known for its use in both milk and meat production. However, the mechanisms underlying color variation in the abdominal adipose tissue of this breed remain poorly understood. In this study, the sequencing of non-coding RNAs (ncRNAs) was conducted on abdominal adipose tissue of different colors from Kazakh horses, with the aim of investigating the molecular mechanisms responsible for this variation. A total of 205 differentially expressed long non-coding RNAs (DELncRNAs) including ENSECAG00000003836, ENSECAG00000017858, and ENSECAG00000035167; 52 differentially expressed microRNAs (DEmiRNAs) including miR-200-y and eca-miR-9a; and 559 differentially expressed circular RNAs (DEcircRNAs) including ZNF226 and ITPKC, were identified between Group W and Group Y. GO annotation and KEGG enrichment analyses of the DEGs revealed that these genes were primarily involved in biological processes such as chemical homeostasis (biological process, BP), intracellular components (cellular component, CC), and iron-sulfur cluster binding (molecular function, MF) as well as in metabolic pathways related to lipid biosynthesis and metabolism including vitamin B6 metabolism, tryptophan metabolism, and glycerolipid metabolism. The sequencing accuracy was further validated using reverse transcription quantitative PCR (RT-qPCR). This study identified key DEGs and signaling pathways associated with the color variation in adipose tissue of Kazakh horses and sheds light on the regulatory genes and biological processes involved. These findings provide a theoretical basis and research foundation for future studies on color variations in the adipose tissue of equine species. Full article

Long non-coding RNAs (lncRNAs) are key regulators of genetic networks in numerous biological processes. Micro-nanoplastics represent a novel abiotic stress, having a direct xenobiotic impact on plant cells, while the regulation of lncRNAs in Arabidopsis thaliana under this kind of abiotic stress remains largely unclear. We explored RNA-seq data sets of A. thaliana roots treated with two types of micro-nanoplastics: transparent polyethylene terephthalate (Tr-PET) and blue polyethylene terephthalate (Bl-PET) to reveal known and new unannotated lncRNAs. Our findings showed that the Tr-PET changed the expression of 104 lncRNAs, while the Bl-PET changed the expression of just 19. We speculate on the possible significance of the differential expressions for plant tolerance and resistance to micro-nanoplastic stress. A key finding of this work is that the studied lncRNAs tend to regulate their neighboring protein-coding genes. Consistent with this regulatory role, their promoters were found to contain cis-acting regulatory elements responsive to abscisic acid, light, MeJA, MYC/MYB, and other stress-related signals. Furthermore, some of the miRNAs that participate in plant development and defense were also predicted to be sponged by the differentially expressed lncRNAs. In summary, this study adds to our knowledge of A. thaliana lncRNAs through the discovery of new transcripts, describing their expression under micro-nanoplastic stress, and revealing their possible roles in post-transcriptional gene regulation. Full article

Deregulation of microRNAs (miRNAs) has been implicated in the development of inflammatory bowel disease (IBD). Specific miRNAs are differentially expressed in patients with IBD compared to healthy individuals. Regulation of their expression can modulate the inflammatory response, the composition of the intestinal microbiota, and intestinal barrier function. miRNAs can regulate the immune and inflammatory response via multiple mechanisms, from Th1/Th17 regulation and ferroptosis to modulation of NLRP3 (NOD-like receptor family, pyrin domain-containing 3) and control of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway. The use of miRNAs as biomarkers and therapeutic targets may help monitor IBD treatment and support the development of new, more individualized therapies that minimize common side effects. Full article

The present study provides a detailed review of cardiovascular biomarkers critical for the diagnosis, prognosis, and pathophysiology of cardiovascular diseases, the leading cause of global morbidity and mortality. These biomarkers aid in detecting disease onset, progression, and therapeutic responses, providing insights into molecular mechanisms. Enzyme markers like AST, CK-MB, LDH, CA-III, and HBDH are pivotal for detecting myocardial injury during acute events. Protein markers such as CRP, H-FABP, and MPO shed light on inflammation and oxidative stress. Cardiac Troponins, the gold standard for myocardial infarction diagnosis, exhibit high specificity and sensitivity, while IMA and GPBB indicate ischemia and early myocardial damage. Peptide markers, including BNP and NT-proBNP, are crucial for heart failure diagnosis and management, reflecting ventricular stress and remodeling. Novel peptides like MR-proANP and MR-proADM aid in assessing disease severity. Lipid markers such as lipoprotein-associated phospholipase A2 and oxylipins provide insights into lipid metabolism and atherosclerosis. Inflammatory and stress-related biomarkers, including TNFα, IL-6, GDF-15, and Pentraxin 3, illuminate chronic inflammation in CVDs. Hormonal markers like copeptin and endothelin-1 highlight neurohormonal activation, while emerging markers such as ST2, galectin-3, PAPP-A, and TMAO elucidate fibrosis, remodeling, and metabolic dysregulation. The inclusion of microRNAs and long non-coding RNAs represents a breakthrough in biomarker research, offering sensitive tools for early detection, risk stratification, and therapeutic targeting. This review emphasizes the diagnostic and prognostic utility of these biomarkers, advancing cardiovascular care through personalized medicine. Full article

Background: ZDHHC19—a protein acyltransferase—is known to be induced in sepsis, a dysregulated immune response to infection, but the underlying molecular mechanisms remain elusive. In this study, we aimed to explore whether upregulation of ZDHHC19 is modulated by single nucleotide polymorphisms (SNPs) affecting the binding of microRNA in the 3’ untranslated region of the gene. Methods: Inpatients with clinically verified severe infection (n = 83) or sepsis (n = 63) were recruited to the study. Genomic DNA and total RNA were prepared from buccal and peripheral blood samples, respectively. Genotyping of rs112579116 and rs2293161 SNPs was performed by TaqMan real-time PCR assays, while ZDHHC19 mRNA as well as miR-4733 and -596 microRNA levels were quantitated by reverse transcription qPCR. Correlations between genotypes, expression levels and clinical parameters were assessed by the Shapiro–Wilk, Mann–Whitney and t-tests. Results: Transcript levels of ZDHHC19 were significantly enhanced in septic blood samples (p = 0.0000709) and associated with clinical parameters such as procalcitonin levels, blood cell counts and clotting factors. Levels of both miRNAs showed an inverse but not significant correlation with those of ZDHHC19. Conclusions: Expression of ZDHHC19 should be considered a reliable molecular marker of sepsis, but further investigations are needed to shed light on regulatory mechanisms involved. Full article

Background: Phospholipase A (PLA) enzymes catalyze the hydrolysis of glycerophospholipids, releasing free fatty acids and lysophospholipids that play vital roles in plant growth, development, and stress responses. Methods: This study identified and analyzed SlPLA genes through bioinformatics and further explored the function of PLA genes under cold stress through virus-induced gene silencing (VIGS) experiments. Results: This study systematically characterized the SlPLA gene family in tomato, identifying 80 genes distributed across 12 chromosomes. Phylogenetic analysis categorized these genes into three groups: pPLA, PLA1, and PLA2. Conserved motifs and gene structure analysis revealed distinct patterns, with some genes lacking untranslated regions (UTRs), which suggests functional diversification. Promoter analysis indicated that SlPLA genes are regulated by light, hormones, and stress-related elements, particularly cold stress. RNA-seq data and qRT-PCR results indicated the differential expression of SlPLA genes across various tissues in tomato cultivars (Heinz and Micro-Tom). Under cold stress, certain SlPLA genes, especially SlPLA1-2, were up-regulated, suggesting their involvement in cold tolerance. Silencing SlPLA1-2 resulted in increased membrane damage, elevated malondialdehyde (MDA) levels, higher electrolyte leakage, and a lower expression of cold-responsive genes within the ICE1-CBF-COR pathway and jasmonic acid (JA) biosynthesis. Conclusions: This study discovered 80 SlPLA genes in tomato across 12 chromosomes, categorizing them into pPLA, PLA1, and PLA2 via phylogenetic analysis. The qRT-PCR analysis identified that SlPLA1-2 was strongly induced by cold stress, and further experiments regarding genetics and physiology revealed that SlPLA1-2 boosts the cold tolerance of tomato by affecting the CBF signaling pathway and JA biosynthesis, offering insights for future stress-resilience breeding. Full article

Cultivated persimmon (Diosspyros kaki Thunb.) is a hexaploid (mostly) or a nonaploid with high heterozygosity, hindering molecular genetic studies on proanthocyanidin (PA) metabolism, which is a major trait for persimmon astringency. Recently, one of its wild diploid relative species, oily persimmon (Diospyros oleifera), has been assembled with a chromosome-level reference. Thus, oily persimmon is now regarded as a model plant for discovering new genes associated with PA metabolism, which is highly accumulated in the fruits of this genus. In our study, we identified genome-wide microRNAs (miRNAs) and their precursor sequence based on the chromosome-scale genome of oily persimmon and the miRNA database of “Eshi 1” according to the sequence alignment and secondary structure accession. The targets were predicted on the psRNATarget software based on the genome CDS database. The size, conservation, diversity, stem-loop hairpin structures, and genome location of miRNA or the precursor sequence were analyzed by bioinformatics tools. The promoter elements of the miRNA genes were predicted on the promoter-2.0 software, which indicated that the abundant cis-acting elements were light responsiveness, promoter, and enhancer regions. The qRT-PCR assay was performed to elucidate the potential expression patterns of precursor miRNA and their targets during fruit development, and one target gene, DkMYB22, of miR2911 was verified to promote the conversion of soluble tannins into insoluble tannins involved in the deastringency in persimmons. Together, this study provides a robust foundation for further functional verification of these miRNAs associated with the natural deastringency process in persimmon, thereby facilitating advancements in persimmon fruit breeding. Full article

The emergence of sustained neuropsychiatric symptoms (NPS) among non-demented individuals in later life, defined as mild behavioral impairment (MBI), is linked to a higher risk of cognitive decline. However, the underlying pathophysiological mechanisms remain largely unexplored. A growing body of evidence has shown that MBI is associated with alterations in structural and functional neuroimaging studies, higher genetic predisposition to clinical diagnosis of Alzheimer’s disease (AD), as well as amyloid and tau pathology assessed in the blood, cerebrospinal fluid, positron-emission tomography (PET) imaging and neuropathological examination. These findings shed more light on the MBI-related potential neurobiological mechanisms, paving the way for the development of targeted pharmacological approaches. In this review, we aim to discuss the available clinical evidence on the role of amyloid and tau pathology in MBI and the potential underlying pathophysiological mechanisms. Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, disruption of neurotrophic factors, such as the brain-derived neurotrophic factor (BDNF), abnormal neuroinflammatory responses including the kynurenine pathway, dysregulation of transforming growth factor beta (TGF-β1), epigenetic alterations including micro-RNA (miR)-451a and miR-455-3p, synaptic dysfunction, imbalance in neurotransmitters including acetylcholine, dopamine, serotonin, gamma-aminobutyric acid (GABA) and norepinephrine, as well as altered locus coeruleus (LC) integrity are some of the potential mechanisms connecting MBI with amyloid and tau pathology. The elucidation of the underlying neurobiology of MBI would facilitate the design and efficacy of relative clinical trials, especially towards amyloid- or tau-related pathways. In addition, we provide insights for future research into our deeper understanding of its underlying pathophysiology of MBI, and discuss relative therapeutic implications. Full article

TIR1/AFB proteins are a class of auxin receptors with key roles in plant development and biotic and abiotic stress responses; several have been identified as targets of the auxin-mimicking herbicide picloram. In this study, we identified five putative TIR1/AFB gene family members in the important vegetable crop Solanum melongena (eggplant) and characterized them using bioinformatics tools and gene expression analyses. Phylogenetic analysis of the TIR1/AFBs classified them into three subgroups based on their Arabidopsis and Solanum lycopersicum homologs. AFB6 homologs were present only in S. melongena and S. lycopersicum, whereas AFB2/3 homologs were found only in Arabidopsis. One pair of S. melongena TIR1 homologs were located in syntenic regions in the genome and appeared to have arisen by segmental duplication. Promoter analysis revealed 898 cis-elements in the TIR1/AFB promoters, 125 of which were related to hormones, stress, light, or growth responses, but only SmAFB5 had a cis-acting regulatory element involved in auxin responsiveness (AuxRR-core). RNA sequencing and expression profiling showed that the TIR1/AFB genes were differentially expressed at different growth stages and in response to light, temperature, and drought. Only SmTIR1A expression was significantly induced by picloram treatment and different growth stages. TIR1/AFB expression is regulated by microRNAs (miRNAs) in other plant species, and we identified 6 or 29 miRNAs that potentially targeted the five TIR1/AFB genes on the basis of comparisons with S. lycopersicum and S. tuberosum miRNAs, respectively. Three-dimensional protein structure predictions revealed that all the TIR1/AFB proteins were very similar in structure, differing only in the numbers of alpha helices and in one angle linking an α helix and a β sheet. For measuring the function of TIR1/AFB genes in response to drought, SmAFB5 was selected, and knockdown by virus-induced gene silence (VIGS) 35S::SmAFB5 lines showed resistance to drought compared to controls. These analyses provide insight into the potential functions of TIR1/AFBs during growth and in response to stress; they highlight differences among the SmTIR1/AFBs that may be useful for eggplant breeding. Full article

MicroRNAs (miRNAs) are pivotal regulators of gene expression, playing crucial roles in plant developmental processes and environmental responses. However, the function of miRNAs in influencing deciduous traits has been little explored. Here, we utilized sRNA-seq on two deciduous species, Ilex polyneura (Hand.-Mazz.) S. Y. Hu and Ilex asprella Champ. ex Benth., along with an evergreen species, Ilex latifolia Thunb., to identify and annotate miRNAs within these species. Our analysis revealed 162 species-specific miRNAs (termed SS-miRNAs) from 120 families, underscoring the fundamental roles and potential influence of SS-miRNAs on plant phenotypic diversity and adaptation. Notably, three SS-miRNAs in I. latifolia were found to target crucial genes within the abscission signaling pathway. Analysis of cis-regulatory elements suggested a novel regulatory relationship that may contribute to the evergreen phenotype of I. latifolia by modulating the abscission process in a light-independent manner. These findings propose a potential mechanism by which SS-miRNAs can influence the conserved abscission pathway, contributing to the phenotypic divergence between deciduous and evergreen species within the genus Ilex. Full article

MiR399 plays an important role in plant growth and development. The objective of the present study was to elucidate the evolutionary characteristics of the MIR399 gene family in grapevine and investigate its role in stress response. To comprehensively investigate the functions of miR399 in grapevine, nine members of the Vvi-MIR399 family were identified based on the genome, using a miRBase database search, located on four chromosomes (Chr 2, Chr 10, Chr 15, and Chr 16). The lengths of the Vvi-miR399 precursor sequences ranged from 82 to 122 nt and they formed stable stem–loop structures, indicating that they could produce microRNAs (miRNAs). Furthermore, our results suggested that the 2 to 20 nt region of miR399 mature sequences were relatively conserved among family members. Phylogenetic analysis revealed that the Vvi-MIR399 members of dicots (Arabidopsis, tomato, and sweet orange) and monocots (rice and grapevine) could be divided into three clades, and most of the Vvi-MIR399s were closely related to sweet orange in dicots. Promoter analysis of Vvi-MIR399s showed that the majority of the predicted cis-elements were related to stress response. A total of 66.7% (6/9) of the Vvi-MIR399 promoters harbored drought, GA, and SA response elements, and 44.4% (4/9) of the Vvi-MIRR399 promoters also presented elements involved in ABA and MeJA response. The expression trend of Vvi-MIR399s was consistent in different tissues, with the lowest expression level in mature and young fruits and the highest expression level in stems and young leaves. However, nine Vvi-MIR399s and four target genes showed different expression patterns when exposed to low light, high light, heat, cold, drought, and salt stress. Interestingly, a putative target of Vvi-MIR399 targeted multiple genes; for example, seven Vvi-MIR399s simultaneously targeted VIT_213s0067g03280.1. Furthermore, overexpression of Vvi_MIR399e and Vvi_MIR399f in Arabidopsis enhanced tolerance to drought compared with wild-type (WT). In contrast, the survival rate of Vvi_MIR399d-overexpressed plants were zero after drought stress. In conclusion, Vvi-MIR399e and Vvi-MIR399f, which are related to drought tolerance in grapevine, provide candidate genes for future drought resistance breeding. Full article

Currently, only a limited set of molecular traits are utilized to direct treatment for metastatic CRC (mCRC). The molecular classification of CRC depicts tumor heterogeneity based on gene expression patterns and aids in comprehending the biological characteristics of tumor formation, growth and prognosis. Additionally, it assists physicians in tailoring the therapeutic approach. Microsatellite instability (MSI-H)/deficient mismatch repair proteins (MMRd) status has become a ubiquitous biomarker in solid tumors, caused by mutations or methylation of genes and, in turn, the accumulation of mutations and antigens that subsequently induce an immune response. Immune checkpoint inhibitors (ICI) have recently received approval for the treatment of mCRC with MSI-H/MMRd status. However, certain individuals experience either initial or acquired resistance. The tumor-programmed cell death ligand 1 (PD-L1) has been linked to the ability of CRC to evade the immune system and promote its growth. Through comprehensive research conducted via the PUBMED database, the objectives of this paper were to review the molecular characteristics linked to tumor response in metastatic CRC in light of improved patients’ outcomes following ICI therapies as seen in clinical trials and to identify particular microRNAs that can modulate the expression of specific oncoproteins, such as PD-L1, and disrupt the mechanisms that allow the immune system to be evaded. Full article