Search Results (1,046)

Cervical cancer (CCa) is the fourth leading cause of cancer-related deaths among women worldwide, with nearly 90% of cases in low- and middle-income countries, especially in Sub-Saharan Africa. This study explores the roles of circular ribonucleic acids (circRNAs), hsa_circ_0001038 and circRNA_400029, and the impact of the serine/arginine-rich splicing factor 3 (SRSF3) inhibitor, theophylline, in CCa cell lines. We utilized cell cycle fluorescence-activated cell sorting (FACS) and Annexin V/propidium iodide (PI) assays to evaluate theophylline’s effects on SiHa and C33A cell lines. Results showed S-phase arrest in SiHa and G2/M arrest in C33A, with significant cytotoxic effects indicated by apoptosis analysis. Using CircAtlas, we identified micro ribonucleic acids (miRNAs) binding to hsa_circ_0001038, particularly miR-205-5p, which has a tumour-suppressive role. miRTarBase identified miR-16-5p as a key interacting miRNA for circRNA_400029. We constructed a competing endogenous ribonucleic acid (ceRNA) network, revealing multiple miRNA targets. Pathway analysis via the Kyoto Encyclopedia of Genes and Genomes (KEGG) highlighted critical signalling pathways involved in CCa oncogenesis. In conclusion, theophylline demonstrates cytotoxicity in CCa cells, suggesting its potential for repurposing in CCa theranostics, though further optimization is necessary. Full article

Salt stress is a major form of abiotic stress that disrupts soybean germination and early seedling establishment. In this study, physiological, biochemical, and transcriptomic analyses—including germination index, antioxidant enzyme activity, and RNA-seq profiling—were conducted during soybean germination to elucidate early responses to salt stress and biostimulant treatment. A preliminary screening of six biostimulants (nanoparticle zinc oxide (NP-ZnO), nanoparticle silicon dioxide (NP-SiO₂), silicon dioxide (SiO₂), glucose, humic acid, and fulvic acid) revealed NP-SiO₂ as the most effective in promoting germination under salt stress. Under 150 mM NaCl, NP-SiO₂ increased the germination rate and length of the radicle compared with the control, also enhancing peroxidase and ascorbate peroxidase activities while reducing malondialdehyde accumulation, suggesting alleviation of oxidative stress. RNA sequencing revealed extensive transcriptional reprogramming under salt stress, identifying 4579 differentially expressed genes (DEGs) compared with non-stress conditions, while NP-SiO₂ treatment reduced this number to 2734, indicating that NP-SiO₂ mitigated the transcriptional disturbance caused by salt stress and stabilized gene expression networks. Cluster analysis showed that growth- and hormone-related genes suppressed by salt stress were restored under NP-SiO₂ treatment, whereas stress-responsive genes that were induced by salt were attenuated. Hormone-related DEG analysis revealed that NP-SiO₂ down-regulated the overactivation in the abscisic acid, jasmonic acid, and salicylic acid pathways while partially restoring gibberellin, auxin, cytokinin, and brassinosteroid signaling. Overall, NP-SiO₂ at 100 mg/L mitigated salt-induced oxidative stress and promoted early soybean growth by fine-tuning physiological and transcriptional responses, representing a promising nano-based biostimulant for enhancing salt tolerance in plants. Full article

Background: Renal ischemia–reperfusion (I/R) injury represents a principal etiologic factor in acute kidney injury (AKI), in which ferroptosis plays a critical role. Mulberrin (Mul), a prenylated flavonoid with antioxidative properties, has an as-yet undefined role in renal I/R injury. Methods: We established a mouse renal IRI model and an HK-2 H/R system. Renal function, histological injury, oxidative stress, ferroptosis markers, and mitochondrial function were assessed. The role of Sirtuin 3 (Sirt3) in Mul-mediated effects was further examined using siRNA knockdown in HK-2 cells. Results: The administration of Mul led to a marked improvement in renal function, lessened tubular injury, and reduced apoptosis in IRI mice. Mul also restored GSH levels, decreased MDA and Fe²⁺ accumulation, and normalized expression of ferroptosis-related proteins, thereby suppressing ferroptosis. In H/R-injured HK-2 cells, Mul restored mitochondrial membrane potential, increased ATP production, and reduced ROS accumulation. Mechanistically, Mul markedly upregulated Sirt3 expression, and silencing Sirt3 abolished its antioxidant and anti-ferroptosis effects, confirming the essential role of Sirt3 in Mul-mediated protection. Conclusions: Our findings underscore Mul’s therapeutic promise in acute kidney injury and provide a mechanistic foundation for interventions directed at the Sirt3–ferroptosis pathway to safeguard renal function. Full article

Fungal effectors play an important role in plant immunity. The Magnaporthe oryzae effector PWL2 plays a significant role in rice blast disease caused by this fungus. However, the function of PWL2 in rice immunity is not fully understood. In this study, transgenic rice lines overexpressing PWL2 showed resistance to rice blast. Subcellular localization showed that PWL2-GFP fusion protein is localized on the plasma membrane and cytoplasm. Salicylic acid (SA) induces rice resistance to M. oryzae. Notably, the expression of the NPR1 gene exhibited a rhythmic pattern during the early stages of M. oryzae infection in the transgenic rice lines. However, during later stages of infection, transgenic plants showed reduced levels of the NPR1, WRKY45, PR1a and PR10a genes, along with decreased H₂O₂ accumulation, while SA levels remained unchanged. Transcriptome analysis revealed that SA treatment induced the expression of the ARGONAUTE11 (AGO11) gene in rice. Furthermore, during the later infection stage in the transgenic rice lines, the expression levels of both AGO11 and PWL2 genes increased. Intriguingly, PWL2-derived small interfering RNAs (siRNA) were detected in these transgenic rice lines. It suggests that both the SA signaling pathway and PWL2-derived siRNAs function in rice resistance to blast disease caused by M. oryzae. Full article

Background/Objective: Cellular senescence is increasingly recognized as a key mechanism underlying sarcopenia, an age-related muscle disorder with no effective therapeutic. 6,4′-Dihydroxy-7-methoxyflavanone (DMF), a flavonoid isolated from Dalbergia odorifera T. Chen, has shown anti-senescence potential. This study aimed to investigate the protective effects of DMF against myoblasts senescence and elucidate the underlying molecular mechanisms. Method: A cellular model of senescence was established in C2C12 myoblasts using D-galactose (D-gal). The effects of DMF pretreatment were evaluated by assessing senescence phenotypes, myogenic differentiation, and mitochondrial function. The role of Sirtuin3 (SIRT3) was confirmed using siRNA-mediated knockdown. Results: DMF Pre-treatment effectively attenuated D-gal-induced senescence, as indicated by restored proliferation, reduced senescence-associated β-galactosidase activity, decreased DNA damage, and the downregulation of p53, p21^Cip1/WAF1 and p16^INK4a. Furthermore, DMF rescued myogenic differentiation capacity, enhancing the expression of Myoblast determination protein 1, Myogenin, Myosin heavy chain and Muscle-specific regulatory factor 4, and promoting myotube formation. Mechanistically, DMF was identified as a SIRT3 activator. It enhanced SIRT3 expression and activity, leading to the deacetylation and activation of the mitochondrial antioxidant enzyme superoxide dismutase 2. This consequently reduced mitochondrial reactive oxygen species, improved mitochondrial membrane potential and ATP production, and suppressed the NF-κB pathway by inhibiting IκBα phosphorylation and p65 acetylation/nuclear translocation. Crucially, all the beneficial effects of DMF—including oxidative stress reduction, mitochondrial functional recovery, anti-inflammatory action, and ultimately, the attenuation of senescence and improvement of myogenesis—were abolished upon SIRT3 knockdown. Conclusions: Our findings demonstrate that DMF alleviates myoblasts senescence and promotes myogenic differentiation by activating the SIRT3-SOD2 pathway, thereby reducing oxidative stress and NF-κB-driven inflammation responses. DMF emerges as a promising therapeutic candidate for sarcopenia. Full article

In poultry production, the laying rate is a critical economic trait, as high egg production significantly enhances profitability. Mitogen-activated protein kinase-activated protein kinase 3 (MK3) is a member of the mitogen-activated protein kinase (MAPK) family, which plays an important role in follicular development. Our previous RNA-seq analysis revealed that MK3 expression was significantly altered in the ovaries of laying hens exposed to normal versus light-deprivation conditions. Based on previous RNA-seq analysis of chicken ovaries, this study focused on the MK3 gene to explore its role in regulating apoptosis of follicular granulosa cells in laying hens. The results demonstrated that MK3 overexpression induced granulosa cell apoptosis by modulating the expression of key proliferation- and apoptosis-related genes, including FAS, Caspase3, BCL2, and C-myc. These findings were further validated using specific siRNA-mediated knockdown of MK3. Flow cytometry, CCK-8, and EdU assays consistently showed that MK3 facilitated apoptosis and inhibited granulosa cell proliferation. Additionally, dual-luciferase reporter assays revealed that the transcription factor WT1 bound to the MK3 promoter and enhanced its transcriptional activity. Mechanistically, MK3 regulated granulosa cell apoptosis through the TNF/P38 MAPK pathway. This conclusion was corroborated by treatment with the P38 inhibitor GS-444217 and specific siRNA targeting components of the pathway. In summary, MK3 promotes granulosa cell apoptosis in the follicles of laying hens, is transcriptionally regulated by WT1, and exerts its pro-apoptotic effects via the TNF/P38 MAPK pathway. Full article

Early B-cell development is primarily regulated at the transcriptional level and comprises the consecutive differentiation stages B-cell progenitor, pro-B-cell and pre-B-cell. These entities provide the cells of origin in B-cell precursor acute lymphoid leukemia (BCP-ALL) that show aberrations of developmental transcription factors (TFs), representing major oncogenic drivers. Analysis of physiological TFs in these developmental entities helps us to understand their normal and disturbed activities and regulatory connections. Here, we focused on NKL-subclass homeodomain TF NKX6-3, which is active in both normal B-cell progenitors and TCF3::PBX1 fusion gene-positive BCP-ALL cases. By performing siRNA-mediated knockdown and forced expression experiments in BCP-ALL model cell lines, we established a gene regulatory network for NKX6-3 together with TALE-class homeodomain TFs IRX1 and MEIS1, as well as ETS-TF SPIB. Importantly, NKX6-3 was activated by TCF3::PBX1, underlying their co-expression in BCP-ALL. Furthermore, comparative expression profiling analysis of public BCP-ALL patient data revealed TGFb-pathway in-hibitor CD109 as a downregulated target gene of NKX6-3. TGFb-signalling, in turn, enhanced NKX6-3 expression, indicating mutual activation. Finally, RNA-seq analysis of BCP-ALL cell line RCH-ACV after NKX6-3 knockdown revealed MPP7 as an upregulated target gene of both NKX6-3 and TCF3::PBX1, revealing a role for the HIPPO-pathway in B-cell progenitors and TCF3::PBX1-positive BCP-ALL. Collectively, our data introduce novel players and regulatory connections to normal and aberrant TF-networks in B-cell progenitors to serve as potential diagnostic markers or therapeutic targets. Full article

Alzheimer’s disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline and neuropathological hallmarks, including amyloid-β (Aβ) plaques, neurofibrillary tangles (NFTs), and neurodegeneration. Since the amyloid cascade hypothesis was proposed, Aβ has remained a central therapeutic target, with interventions aiming to reduce Aβ production, aggregation, or downstream toxicity. This review first outlines the historical development of the Aβ hypothesis and the two major APP processing pathways (α-cleavage and β-cleavage), highlighting the role of biomarkers in early diagnosis, patient stratification, and regulatory approval. We then summarize the development and clinical outcomes of anti-Aβ small-molecule drugs, including β-secretase inhibitors, γ-secretase modulators, Aβ aggregation inhibitors, receptor/synapse modulators, and metabolic or antioxidant modalities. We further review the progression of biologic therapies, with a particular focus on monoclonal antibodies, vaccines, and emerging gene-silencing strategies, such as small interfering RNA (siRNA) and antisense oligonucleotides. Finally, we discuss future perspectives, including next-generation biologics, multi-target approaches, optimized delivery platforms, and early-prevention strategies. Collectively, these efforts underscore both the challenges and opportunities in translating anti-Aβ therapies into meaningful clinical benefits for patients with AD. Full article

Recent advances in molecular biology have led to the development of RNA-based therapeutics, offering significant promise for treating various eye diseases. Current RNA therapeutics include RNA aptamers, antisense oligonucleotides (ASOs), small interfering RNA (siRNA), and messenger RNA (mRNA) that can target specific genetic and molecular pathways involved in eye disorders. In addition to their potential in therapy, RNA technologies have also provided tools for mechanistic studies to improve the understanding of eye diseases, expanding the possibilities of RNA-based treatments. Despite the utility of RNA in studying eye disease mechanisms and its potential in disease treatment, only a few RNA-based therapies have been approved for posterior eye diseases. This paper reviews RNA interference and related ocular delivery and posterior eye diseases, focusing on the use of RNA aptamers, siRNA, short hairpin RNA (shRNA), and microRNA (miRNA). Approaches using RNA to advance our understanding of eye diseases and disease treatments, particularly in the posterior segment of the eye, are discussed. It is concluded that RNA therapeutics offer a novel approach to treating a variety of eye diseases by targeting their molecular causes. siRNA, shRNA, miRNA, and ASO can directly silence disease-driving genes, while RNA aptamers bind to specific targets. Although many RNA-based therapies are still in experimental stages, they hold promise for conditions such as age-related macular degeneration (AMD), diabetic macular edema (DME), glaucoma, and inherited retinal disorders. Effective delivery methods and long-term safety are key challenges that need to be addressed for these treatments to become widely available. Full article

Drought is a leading constraint on plant productivity and will intensify with climate change. Plant acclimation emerges from a multilayered regulatory system that integrates signaling, transcriptional reprogramming, RNA-based control, and chromatin dynamics. Within this hierarchy, non-coding RNAs (ncRNAs) provide a unifying regulatory layer; microRNAs (miRNAs) modulate abscisic acid and auxin circuits, oxidative stress defenses, and root architecture. This balances growth with survival under water-deficient conditions. Small interfering RNAs (siRNAs) include 24-nucleotide heterochromatic populations that operate through RNA-directed DNA methylation, which positions ncRNA control at the transcription–chromatin interface. Long non-coding RNAs (lncRNAs) act in cis and trans, interact with small RNA pathways, and can serve as chromatin-associated scaffolds. Circular RNAs (circRNAs) are increasingly being detected as responsive to drought. Functional studies in Arabidopsis and maize (e.g., ath-circ032768 and circMED16) underscore their regulatory potential. This review consolidates ncRNA biogenesis and function, catalogs drought-responsive modules across model and crop species, especially cereals, and outlines methodological priorities, such as long-read support for isoforms and back-splice junctions, stringent validation, and integrative multiomics. The evidence suggests that ncRNAs are tractable entry points for enhancing drought resilience while managing growth–stress trade-offs. Full article

Heat stress induces metabolic adaptations in fish, including the regulation of triglyceride (TG) synthesis/degradation to preserve cellular lipid balance and energy homeostasis. Diacylglycerol acyltransferase (DGAT) catalyzes the final step in TG synthesis. However, the molecular mechanisms by which DGAT regulates TG metabolism in heat-stressed fish remain unexplored. Our previous study suggested that miR-10c regulates dgat2 expression in genetically improved farmed tilapia (GIFT, Oreochromis niloticus) under heat stress. Here, we characterized the GIFT miR-10c precursor as a 65-nucleotide transcript yielding a 22 nt mature miRNA (oni-miR-10c). A phylogenetic analysis revealed a high level of miR-10c sequence conservation across species. A dual-luciferase reporter assay confirmed dgat2 as a direct target of miR-10c. Overexpression of miR-10c in vivo down-regulated dgat2 transcripts and DGAT2 protein. SiRNA-knockdown of dgat2 resulted in upregulation of cpt1α, fas, and lpl and downregulation of hsl, thereby reprogramming lipid metabolism in GIFT hepatocytes. Thus, the miR-10c-dgat2 regulatory axis facilitates TG hydrolysis and promotes fatty acid metabolism under heat stress. Our findings highlight miR-10c’s potential as a dgat2 inhibitor and its function in regulating lipid metabolism in heat-stressed GIFT. Our study reveals a key molecular pathway mediating thermal adaptation of energy metabolism in fish, providing novel targets for preventing heat-induced metabolic disorders. Full article

Plants have evolved a complex, multilayered immune system that integrates molecular recognition, signaling pathways, epigenetic regulation, and small RNA-mediated control. Recent studies have shown that DNA-level regulatory mechanisms, such as RNA-directed DNA methylation (RdDM), histone modifications, and chromatin remodeling, are critical for modulating immune gene expression, allowing for rapid and accurate pathogen-defense responses. The epigenetic landscape not only maintains immunological homeostasis but also promotes stress-responsive transcription via stable chromatin modifications. These changes contribute to immunological priming, a process in which earlier exposure to pathogens or abiotic stress causes a heightened state of preparedness for future encounters. Small RNAs, including siRNAs, miRNAs, and phasiRNAs, are essential for gene silencing before and after transcription, fine-tuning immune responses, and inhibiting negative regulators. These RNA molecules interact closely with chromatin features, influencing histone acetylation/methylation (e.g., H3K4me3, H3K27me3) and guiding DNA methylation patterns. Epigenetically encoded immune memory can be stable across multiple generations, resulting in the transgenerational inheritance of stress resilience. Such memory effects have been observed in rice, tomato, maize, and Arabidopsis. This review summarizes new findings on short RNA biology, chromatin-level immunological control, and epigenetic memory in plant defense. Emerging technologies, such as ATAC-seq (Assay for Transposase-Accessible Chromatin using Sequencing), ChIP-seq (Chromatin Immunoprecipitation followed by Sequencing), bisulfite sequencing, and CRISPR/dCas9-based epigenome editing, are helping researchers comprehend these pathways. These developments hold an opportunity for establishing epigenetic breeding strategies that target the production of non-GMO, stress-resistant crops for sustainable agriculture. Full article

Glaesserella parasuis (G. parasuis), a common pathogenic bacterium in the porcine respiratory tract, can cause porcine polyserositis, arthritis, and meningitis. Alveolar macrophages are the first line of defense in the pulmonary innate immunity, and their abnormal apoptosis plays a critical role in the pathogenic process of G. parasuis. Long non-coding RNA maternally expressed gene 3 (MEG3) is associated with G. parasuis infection, but its mechanism remains incompletely unclear. This study aimed to investigate the role of MEG3 in G. parasuis-induced apoptosis of the porcine alveolar macrophage cell line 3D4/21 and its detailed molecular mechanism. Here, we found that MEG3 overexpression promoted G. parasuis-induced apoptosis and upregulated key extrinsic pathway proteins caspase-8 (CASP8) and caspase-3 (CASP3). Mechanistically, MEG3 functioned as a competing endogenous RNA by sponging ssc-miR-135, which directly targets and inhibits CASP8. Consequently, MEG3 overexpression alleviated ssc-miR-135-mediated repression of CASP8. Functional rescue experiments confirmed that either ssc-miR-135 mimic or CASP8 siRNA reversed the pro-apoptotic effect of MEG3. In conclusion, this study reveals that MEG3 relieves the inhibitory effect of ssc-miR-135 on CASP8 through competitively binding, thereby regulating G. parasuis-induced apoptosis of 3D4/21 cells. This study provides new insights into the pathogenic molecular mechanism of G. parasuis. Full article

Objective: Molecular biology techniques were employed to investigate the effects of thrombospondin-4 (Thbs4) expression in dorsal root ganglion (DRG) on peripheral nerve injury repair and regeneration, as well as to elucidate the underlying molecular mechanisms. Methods: A sciatic nerve transection model in rat was established to analyze Thbs4 expression and localization in DRG tissues after injury. Both siRNA and adeno-associated virus (AAV) were used to knockdown or overexpress Thbs4. The effects of knockdown and overexpression of Thbs4 on axon growth were assessed using immunofluorescence staining. The roles of Thbs4 in peripheral nerve injury repair and regeneration were determined using behavioral assays, electrophysiological recordings, and transmission electron microscopy. Results: Thbs4 was primarily localized in the cell membrane and cytoplasm of DRG neurons but was also found in the intercellular spaces. In vitro experiments demonstrated that Thbs4 overexpression promoted axonal regeneration and reduced neuronal apoptosis. They also showed that Thbs4 overexpression accelerated sciatic nerve regeneration and enhanced the recovery of motor and sensory functions. Conversely, Thbs4 knockdown had the opposite effects. This study also showed that the knockdown or overexpression of Thbs4 significantly altered the expression of NF-κB and ERK signaling pathways, suggesting their involvement in peripheral nerve repair and regeneration. Conclusions: Thbs4 expression in DRG tissues is significantly altered following sciatic nerve injury. The NF-κB and ERK may be involved in regulating the repair and regeneration of the peripheral nerve by Thbs4. Full article

Background: A deregulated aldosterone (Aldo)–mineralocorticoid receptor (MR) pathway is linked to cardiovascular disease (CVD), including hypertension and heart failure. Despite the association of elevated plasma Aldo levels with cardiac stress, inflammation, myocardial fibrosis, and cardiac remodeling, the underlying mechanisms remain elusive. Methods: To study the impact of Aldo–MR pathway overactivation on cardiac health, a novel mouse model with AAV9-mediated MR overexpression and Aldo administration via subcutaneous osmotic pumps was generated. Echocardiographic analyses, transcriptome sequencing, and loss-of-function experiments of an identified lead candidate gene were performed. Additionally, cardiac tissue samples from human patients with end-stage heart failure were analyzed in the study. Results: Mice with an overactivated Aldo–MR pathway exhibited increased neutrophil gelatinase-associated lipocalin (NGAL) expression, cardiac dysfunction, hypertrophy, and fibrosis. Transcriptomics identified prostaglandin D₂ synthase (Ptgds) as a novel downstream effector of the cardiac Aldo–MR pathway. SiRNA-mediated inhibition of Ptgds in primary cardiomyocytes reduced NGAL levels and the hypertrophic impact of Aldo, suggesting a role in mediating Aldo-induced cardiac pathologies. Elevated expression of PTGDS was observed in hiPSC-CMs treated with the pro-hypertrophic cytokine leukemia inhibitory factor (LIF) and in end-stage heart failure patients, ascertaining its importance in cardiac disease settings. Conclusions: PTGDS is a newly identified mediator of Aldo–MR-induced cardiac remodeling and may represent a potential therapeutic target for CVD. Full article