Search Results (9,238)

Young barley, derived from the early vegetative stage of Hordeum vulgare L., constitutes a plant-based functional ingredient whose phytochemical profile differs markedly from that of mature grain. Two principal commercial forms exist—dried grass powder and juice-derived products—differing in matrix composition and bioactive compound concentration. This narrative review critically evaluates the current knowledge on the phytochemical composition, biological activity, and translational relevance of young barley preparations considered as a functional plant food. The phytochemical spectrum is dominated by C-glycosyl flavones, particularly saponarin and lutonarin, alongside phenolic acids, chlorophylls, enzymatic antioxidants, vitamins, and minerals. Experimental evidence implicates the modulation of redox homeostasis, inflammatory signaling, and metabolic regulators as the primary biological mechanisms. In vitro studies additionally demonstrate antiproliferative activity in human cancer cell lines and immunomodulatory properties mediated by polysaccharide-rich fractions, extending the biological profile of young barley beyond classical antioxidant activity. Although preclinical models consistently demonstrate antioxidant and metabolic effects, high experimental doses and limited preparation standardization restrict the direct extrapolation to human supplementation contexts. Available clinical trials suggest modest improvements in selected lipid, glycemic, and oxidative stress markers; yet, most are small in scale and brief in duration. Agronomic variables including fertilization strategy and soil composition represent additional, underappreciated sources of phytochemical variability and safety concern. Overall, the current evidence supports the biological plausibility of young barley as a functional plant food; yet, the clinical data remain preliminary. Future research should prioritize preparation standardization, dose–response characterization, and agronomic transparency to strengthen translational reliability. In conclusion, young barley preparations represent a biologically plausible functional plant food ingredient with preliminary clinical support, pending confirmation from adequately powered, standardised randomised controlled trials. Full article

Strigolactones (SLs), as a class of novel plant hormones, play important roles in the regulation of plant branching. However, their function in branch development of wintersweet remains unclear. In this study, a gene involved in SLs biosynthesis, CpD27, was identified and isolated from wintersweet. The sequence characteristics, expression patterns, subcellular localization, and functional analysis through heterologous expression in Arabidopsis thaliana were investigated. Multiple sequence alignment showed that CpD27 contains the conserved D27 protein domain DUF4033. Quantitative real-time PCR analysis revealed that CpD27 is expressed in various vegetative organs of wintersweet, with the highest expression in leaves, followed by axillary buds. It is also expressed in all floral organs, with the highest expression level in the outer petals. CpD27 expression is induced by hormones (ABA and ACC) and low temperature (4 °C). Subcellular localization analysis indicated that CpD27 is localized in the chloroplasts of Arabidopsis. Heterologous expression of CpD27 in Arabidopsis delayed bolting. The number of both rosette branches and cauline branches in transgenic plants was reduced compared with wild-type plants. In addition, the expression of AtBRC1 was significantly upregulated in transgenic lines, suggesting that CpD27 has a function similar to that of its homolog in Arabidopsis. Overall, these results indicate that CpD27 plays a conserved role in the SLs-mediated branching pathway, which regulates branch development in wintersweet. This study provides a molecular and theoretical basis for further understanding branch development in wintersweet. Full article

Early flowering-related factors play pivotal roles in coordinating plant growth and reproductive development. In this study, we investigated the biological function of early flowering gene (ELF) in Arabidopsis thaliana using CRISPR/Cas9-mediated genome editing and construction of overexpression approaches. Two independent ELF overexpression (OE-ELF) and genome-edited (ge-elf) lines were generated and systemically analyzed. ELF overexpression significantly enhanced early seedling performance, increasing germination rate and seedling fresh weight by up to 8.7%, while genome-edited lines exhibited a marked reduction. Root growth was strongly promoted in OE-ELF plants, with root length increase of 85% and 75%, whereas ge-elf lines showed a reduction of up to 48%. At later developmental stages, OE-ELF plants displayed enhanced vegetative growth, including increased leaf length (32%), leaf area (91%), and accelerated flowering (21% earlier than wild type). In contrast, ge-elf delayed flowering by up to 25% and resulted in compact plant architecture. Reproductive development was severely compromised in ge-elf plants, which exhibited malformed inflorescences, reduced pollen germination, shortened silique (45%), and a drastic decrease in seed number per silique (70%). Conversely, OE-ELF plants showed increased silique number and seed per silique. Molecular analysis revealed that ELF positively regulates key flowering-related genes, including FLC, SOC1, AP1, and LFY, which correlated strongly with growth and reproductive traits. Our results demonstrate that ELF functions as a central regulator integrating vegetative growth, floral development, male fertility, and seed production in Arabidopsis thaliana. Full article

Taraxacum kok-saghyz (T. kok-saghyz) is a promising alternative crop for natural rubber production, in which root development is closely associated with rubber synthesis; however, the molecular mechanisms governing root architecture formation remain largely unclear. NAC transcription factors play pivotal roles in plant root development, yet their functions in T. kok-saghyz have not been systematically investigated. In this study, a genome-wide analysis identified 34 NAC family members in T. kok-saghyz. Through transcriptomic analysis following methyl jasmonate (MeJA) treatment, 27 genes significantly responsive to MeJA signaling were screened. Sequence analysis revealed that all TkNAC proteins contain a conserved NAM domain. Subcellular localization assays confirmed that TkNAC16, TkNAC20, TkNAC23, and TkNAC30 are localized to the nucleus. Yeast two-hybrid and bimolecular fluorescence complementation assays demonstrated that TkNAC16/18/20/23/30 can form extensive heterodimers. Overexpression lines of T. kok-saghyz exhibited significantly increased root length, while leaf growth exhibited line- and stage-specific effects. Collectively, this study provides the first systematic identification of the NAC transcription factor family in T. kok-saghyz, elucidates their involvement in methyl jasmonate signaling responses, the construction of heterodimerization networks, and the positive regulation of root elongation. These findings provide crucial genetic resources and a theoretical basis for dissecting the molecular mechanisms underlying the coordinated improvement of root development and rubber yield in T. kok-saghyz. Full article

Major infrastructure investments alter accessibility and urban development patterns, yet their impact on housing prices varies significantly across regions. The prevailing interpretation attributes this heterogeneity to supply differences or regulatory constraints, treating land use regulations as exogenous variables. Nevertheless, even two regions with a nominally similar regulatory framework may produce substantially different outcomes in the housing market, depending on the effectiveness of rule implementation. This paper argues that this approach overlooks a critical variable: the ability of regional authorities to coordinate, regulate, permit, and implement spatial development in a predictable and timely manner. In line with this, a conceptual framework is developed, grounded in the literature on spatial and multi-level governance, in which regional institutional capacity is proposed as a potential mediator of capitalization around project milestones (announcement, funding, construction, operation), rather than as a backdrop. This capacity shapes outcomes through three interrelated dimensions: the responsiveness of supply, which depends on administrative capacity and regulatory consistency; the coherence of governance across jurisdictions within functional urban areas; and the management of land value through land value capture instruments. From this framework, testable propositions are derived regarding the intensity, timing, and spatial distribution of price effects. The study does not empirically estimate changes in housing prices, nor does it test the propositions put forward. Instead, it develops the conceptual framework and organizes the spatial and institutional units of observation required for a subsequent empirical test. The framework is specified spatially through Section A, Line 4 of the Athens Metro to organize the project’s spatial units, administrative jurisdictions, land uses, and milestones for future analysis. The contribution is threefold: conceptual, as it elevates regional institutional capacity from a contextual to an explanatory variable; theoretical, in that it bridges urban economics with the governance literature; and policy-relevant, since it repositions the reform of regional governance as a constituent element of housing policy and as a factor that may shape sustainable spatial development outcomes. Full article

Background: Thromboxane B2 Synthase 1 (THBS1), also known as TSP-1, is a multifunctional glycoprotein involved in various cellular processes that plays a crucial role in skeletal muscle development and repair. It acts as a key physiological activator of transforming growth factor-β1 (TGF-β1), both in vivo and in vitro. Methods: This study aimed to investigate the effects of THBS1 on myoblast proliferation and differentiation using the mouse skeletal muscle satellite cell line C2C12 and to reveal its regulatory relationship with the TGF-β signaling pathway through a series of cellular and molecular experiments. Results: Overexpression or knockout of THBS1 in C2C12 cells regulates and upregulates the activity of the TGF-β signaling pathway, thereby inhibiting the proliferation and differentiation of C2C12 cells. Conclusions: These results provide a theoretical foundation for future research aimed at enhancing skeletal muscle quality in livestock and poultry and lay the groundwork for developing therapeutic strategies for skeletal muscle disorders. Full article

Background/Objectives: Telomeres are critical biomarkers of biological aging, with shortened leukocyte telomere length strongly linked to all-cause mortality and age-related disease risk. Although exercise modulates telomere dynamics, the field’s evolution from descriptive measurements to mechanistic inquiries involving redox biology and epigenetics remains incompletely mapped. This study systematically characterized the global research landscape of telomere–exercise science over 25 years to establish a strategic evidence base for precision exercise prescription. Methods: A bibliometric analysis was conducted on 858 publications from the Web of Science Core Collection (2000–2025). CiteSpace and VOSviewer were used for keyword co-occurrence analysis, strategic thematic mapping, and citation burst detection to visualize global research trends and identify emerging frontiers. Results: Annual publication volume grew from 2 (2000) to 71 (2025), with a compound annual growth rate of 15.4%. China emerged as one of the leading global contributors. Thematic analysis revealed a paradigm shift from descriptive leukocyte telomere length studies toward mechanistic investigations of oxidative stress, mitochondrial homeostasis, and epigenetic clocks. Keyword network analysis confirmed oxidative stress and inflammation as central hubs, mediating telomere protection via redox regulation and non-canonical telomerase functions. Conclusions: Exercise preserves telomere integrity primarily through redox–mitochondrial homeostasis, hormesis-driven antioxidant upregulation, and non-canonical telomerase activation. For aging populations and individuals at metabolic risk, aerobic training and high-intensity interval training (HIIT) are recommended as first-line non-pharmacological interventions for healthspan extension. Leukocyte telomere length and telomerase activity should be integrated as biomarkers in preventive medicine practice. Future large-scale randomized controlled trials incorporating multi-omics approaches and sex-stratified analyses are warranted to establish individualized dose–response guidelines for precision exercise prescription. Full article

PVP-stabilized silver nanoparticles (Ag NPs) were functionalized with sildenafil (Sil), leading to spherical NPs (Ag@Sil NPs) with a size of about 30 nm as observed through transmission electron microscopy and dynamic light scattering. Fourier-transformed IR spectroscopy confirmed the covering of the particles with Sil. The Ag@Sil NPs were incorporated into a 0.1 wt% ointment and tested for the treatment of acute anal fissures in a preliminary medical study involving 50 patients. Typical symptoms such as pain, bleeding, itching, and mass sensation were improved in the intervention group with no adverse effects. Molecular docking showed strong interactions with docking scores slightly above −10 kcal/mol between sildenafil and two different model complexes [Ag–Sil]⁺ for the Ag-bound sildenafil with either piperazine-N- or pyrazole-N-bound Ag⁺ ions and the muscarinic M2 and the nicotinic acetylcholine α3β4 receptor, which are both involved in anal sphincter regulation. All three showed superior binding compared with nitroglycerin and L-arginine. The residue analysis revealed a higher number of relevant interactions for the sildenafil and the two Ag⁺ complexes, compared to nitroglycerin and L-arginine, fully in line with the differences in the docking scores. Full article

Cross-presentation of exogenous antigens by dendritic cells (DCs) relies on the cytosolic pathway, enabling proteasomal processing and subsequent loading of antigenic peptides onto major histocompatibility complex class I (MHC-I) molecules. Although this pathway is central to CD8⁺ T-cell activation, the molecular mechanisms that regulate intracellular antigen processing and redistribution during cross-presentation remain incompletely defined. In this study, we investigated the contribution of the large-pore channel Pannexin-1 (Panx1) to antigen handling during cross-presentation. Using confocal microscopy and quantitative image analysis in granulocyte–macrophage colony-stimulating factor/interleukin-4 (GM-CSF/IL-4)-derived inflammatory bone marrow-derived dendritic cell (BMDC)-like cellsexposed to ovalbumin (OVA)–Alexa Fluor 488, we observed time-dependent changes in intracellular antigen distribution that were altered upon pharmacological inhibition of Panx1 with the blocking peptide 10Panx1. In parallel, functional assays revealed that Panx1 inhibition significantly reduced SIINFEKL peptide-dependentactivation of B3Z CD8⁺ T-cell hybridomas following pulsing with full-length OVA. Similar effects were observed in the cross-presentation-competent MUTU1940 dendritic cell line. Importantly, Panx1 inhibition did not significantly affect dendritic-cell viability or LPS-induced activation under the experimental conditions tested. In contrast, pharmacological inhibition or genetic deficiency of P2X7 receptor (P2X7) did not produce comparable reductions in cross-presentation, and combined inhibition did not result in additive effects under the experimental conditions tested. Together, these findings provide functional evidence supporting a role for Panx1 in regulating intracellular antigen redistribution associated with cross-presentation. While not establishing direct genetic causality, our data identify Panx1 as a modulatory component influencing antigen-processing events that culminate in CD8⁺ T-cell activation, thereby expanding the current framework of intracellular antigen-processing mechanisms involved in dendritic-cell-mediated cross-presentation. Full article

The skin serves as the body’s first line of defense against environmental threats, acting as a barrier between external aggressors and internal systems. Current evidence regarding the roles of sulfur dioxide (SO₂) in biology and medicine is limited. Environmental pollutants, including SO₂, can increase the production of reactive oxygen species in the skin, leading to oxidative damage that may worsen various dermatological conditions. Endogenous SO₂, proposed as the fourth member of the gasotransmitter family, functions as a biological signaling molecule. It is generated in various human skin cells, including vascular smooth muscle cells, endothelial cells, mast cells, keratinocytes, macrophages, adipocytes, fibroblasts, dermal immune cell population, etc, where it performs multiple functions at physiologically relevant concentrations. Endogenous SO₂ plays a crucial role in regulating cell signaling and maintaining skin homeostasis through its antioxidant, anti-inflammatory, and cytoprotective effects. Abnormal generation and metabolism of SO₂ are linked to several critical processes in the skin, including vascular biology, immune response, cell proliferation, pigmentation, malignancy, protective barriers, senescence, and resistance to stress. This paper provides a narrative review of the significant roles of SO₂ in skin health and disease. A comprehensive understanding of the complex molecular effects and mechanisms mediated by SO₂ in human skin, along with the development of gas therapy, will be essential for translating fundamental research into clinical applications. Full article

Background/Objectives: Numerous studies have investigated the responses of the gastrointestinal tract to tastants, particularly in specialized enteroendocrine and other chemosensory cells. However, many of these investigations used various taste stimuli often at high concentrations or relied on immortalized cell lines or heterogeneous cell populations, which can limit their physiological relevance and reproducibility. To establish a stable, physiologically representative model system for consistently investigating gut epithelial responses to tastants, our study developed 3D murine intestinal organoids (MIOs). Methods: Murine intestinal organoids were generated from isolated intestinal crypts and cultured under defined conditions to maintain epithelial differentiation. Organoids were stimulated with selected nutrients and tastants, and downstream signaling responses were assessed using hormone secretion assays. Results: The 3D MIO culture system was successfully established, providing a robust in vitro platform for studying extraoral bitter sensing and release of the enteroendocrine hormone cholecystokinin. Moreover, 5 mM denatonium benzoate and 30 mM L-glutamic acid specifically induced cholecystokinin secretion in MIOs, whereas other bitter or non-bitter stimuli did not. Conclusions: Murine intestinal organoids provide a stable model for studying nutrient- and tastant-evoked signaling in the gut. This approach enables precise investigation of underlying mechanisms and may advance our understanding of gut chemosensation and metabolic regulation. Full article

Background/Objectives: Glucocorticoids, including dexamethasone (DEX), are known to demonstrate anti-inflammatory activity, suppress steroidogenesis, and mitigate the adverse effects of chemotherapy. They are therefore widely employed for managing solid malignancies. Emerging evidence indicates that DEX modulates both systemic and local renin–angiotensin system (RAS) activity, including genomic signaling via the glucocorticoid receptor (GR). Methods: DEX-dependent transcriptional responses for the angiotensin receptor genes (AGTR1, AGTR2, MAS1, and LNPEP) were evaluated in ovarian (SKOV3, KURAMOCHI) and prostate (DU-145, PC3) cancer cell lines. The cells were cultured under different serum conditions to determine the influence of nutrient availability on tumor progression. Results: DEX demonstrated distinct mechanisms of action between the ovarian and prostate cancer models. It was found to promote cancer cell survival through tissue-specific modulation of metabolic activity, clonogenic capacity, cell cycle distribution, and apoptotic responses. These effects were accompanied by condition-dependent alterations in angiotensin receptor gene expression. Hence, DEX may mediate the remodeling of local RAS signaling, which may be significant in overall survival and disease-free survival. The findings also indicate a previously-unreported NR3C1–LNPEP correlation, which was consistently observed across in vitro systems and patient datasets, in both ovarian- and prostate-derived cancer models. Conclusions: DEX appears to exert context-dependent regulation of RAS-associated gene networks in ovarian and prostate cancer, suggesting a role in tumor adaptive responses and potentially in therapeutic contexts. Full article

This study examines the schooling experiences of transgender students in Malta within the broader historical and sociocultural influence of the Catholic religion, focusing on how religious discourse shapes processes of inclusion and exclusion. Drawing on semi-structured interviews with transgender students, parents, educators, and school administrators, the findings reveal that Catholic doctrine and its presence within school contexts contribute to the erasure of transgender identities from early childhood onward. In contrast to ecclesiastical narratives that frame transgender identity as a form of “gender ideology,” participants’ accounts demonstrate that social and medical transitions function as critical strategies for survival, well-being, and self-recognition. Methodologically, the study employs qualitative thematic analysis informed by a critical anticolonial framework, enabling an interrogation of how religious authority intersects with colonial legacies to regulate gender and embodiment. The analysis further highlights tensions between the Catholic religion and contemporary human rights and ethical frameworks, particularly in relation to inclusion. The study concludes that if the Catholic religion is to retain relevance within school contexts, it must undergo a substantive ethical reorientation toward inclusivity, recognizing transgender embodiment and agency. In line with emancipatory pedagogical traditions, this entails reimagining the role of the Catholic religion as one that actively supports social justice, critical consciousness, and transformative practices of inclusion. Full article

The continuous expression of HPV oncogenes E6 and E7 contributes to the maintenance of the cervical cancer (CC) phenotype by altering gene expression programs involved in tumor progression and aggressiveness. MicroRNAs (miRNAs) have emerged as critical regulators of gene expression in CC, including miR-218-5p, which has been described as a tumor suppressor. In this study, we investigated the impact of HPV-16 oncoproteins E6 and E7 on the regulation of miR-218-5p expression and its target gene PIK3C2A, as well as their functional and clinical relevance in CC. We found that miR-218-5p expression is significantly reduced in HPV-16-positive CC cell lines, while PIK3C2A expression is increased. Silencing the expression of the E6/E7 oncogenes in Ca Ski cells restored miR-218-5p levels and reduced PIK3C2A expression. Conversely, overexpression of the E6 and E7 oncogenes in C-33 A cells significantly decreased miR-218-5p expression and increased PIK3C2A expression. Functional assays performed on C-33 A cells expressing E6 and E7 revealed that ectopic expression of miR-218-5p suppresses cell proliferation and migration, effects that are partially mediated by PIK3C2A. Bioinformatics analysis showed that low miR-218-5p expression and high PIK3C2A expression are associated with reduced overall survival in patients with cervical cancer. Our findings identify the miR-218-5p/PIK3C2A axis as a novel regulatory pathway modulated by HPV-16 oncoproteins E6 and E7 that contributes to CC cell proliferation and migration. Furthermore, miR-218-5p and PIK3C2A emerge as potential prognostic biomarkers in CC. Full article

Background/Objectives: The orphan nuclear receptors 4A1 (NR4A1) and NR4A2 are overexpressed in multiple solid tumors, and both receptors exhibit tumor promoter-like activities. A recent study reported that luteolin, a flavonoid that binds NR4A1, decreased the expression of the pro-oncogenic receptor tyrosine kinase MerTK in colon cancer cells. Methods/Results: In this study, we observed that MerTK protein was expressed in human SW480 and HCT116 and mouse CT26 colon cancer cell lines, and was significantly downregulated after treatment with 1,1-bis(3′-indolyl)-1-(3,5-disubstitutedphenyl)methane (DIM-3,5) compounds, which are dual NR4A1/NR4A2 ligands. Moreover, knockdown of NR4A1 and NR4A2 also decreased MerTK protein expression and DIM-3,5 ligands, and receptor knockdown also decreased MerTK RNA levels expression. MerTK expression was also downregulated by knockdown of Sp1, Sp3, or Sp4 and by treatment with mithramycin. Subsequent studies using chromatin immunoprecipitation and transfection of a MERTK (promoter)–luciferase construct containing transcriptionally active GC-rich promoter elements indicated that MerTK expression in colon cancer cells was regulated by NR4A/Sp complexes, including NR4A1, NR4A2, Sp1, Sp3, and Sp4 transcription factors. Conclusions: The participation of NR4A1 and NR4A2 in the regulation of MerTK indicates that DIM-3,5 ligands represent a novel class of agents that can be used to inhibit MerTK expression in cancer cells by acting as dual NR4A1 and NR4A2 inverse agonists. Full article