Search Results (5,964)

Altered extracellular matrix (ECM), a hallmark of solid tumors, affects cellular survival, migration and differentiation. Typically viewed as tumor-suppressive, evidence suggests that apoptosis can also generate pro-tumoral signals. We previously showed that ECM from high-grade astrocytomas induces extensive endothelial anoikis, while a surviving subpopulation fails to form tubular structures (tubulogenesis-defective endothelial cells, or TDECs). We combined functional assays with whole-cell proteomics to investigate this response. Using real-time video microscopy, we found that apoptotic endothelial cells induced by tumor ECM attracted migrating endothelial cells and guided sprouting. Conditioned media from apoptotic endothelial cells contained a 2.8-fold increase in extracellular vesicles (EVs) relative to autologous ECM-primed endothelial cells. Although both EV populations improved TDEC tubulogenesis, only EVs produced upon tumor-ECM stimulation induced TDEC migration—a property lost when using EVs secreted by endothelial cells growing on TN-C-depleted matrices. Proteomic profiling revealed that TDECs shift from an adhesion-anchored to a microtubule-rich and glycolytically rewired phenotype, with upregulation of vesicle-trafficking regulators (ARF1/3/4, ANXA2/5), migration drivers (RAC1/3, RHOA/C, WDR1, FSCN1) and glycolytic enzymes (ENO1, ALDOA, PKM, LDHA), alongside the suppression of integrin- and cytoskeletal-anchoring proteins. Collectively, these findings indicate that tumor-ECM-driven endothelial apoptosis generates reversible reprogramming and an EV-mediated autocrine mechanism that may favor angiogenic balance. Full article

Mulberry (Morus alba) is an economically important forest tree species, yet cutting propagation is constrained by low adventitious rooting efficiency. Although ABT, a composite rooting promoter, can improve cutting survival, its molecular basis remains unclear. Here, cuttings of the cultivar Qiangsang 1 were treated with ABT, NAA, or IAA (200–1000 mg/L) and subjected to transcriptome profiling to elucidate how ABT enhances rooting. Hormone-related analyses showed that ABT upregulated GH3 (auxin-amido synthetase) at days 0 and 20, implicating auxin homeostasis. ERF1/2 (ethylene response factors) exhibited a temporal oscillation, with induction at day 10 followed by repression from days 20 to 30, consistent with a shift from developmental programs to defense-related processes. In parallel, JAZ (jasmonate ZIM-domain) genes were downregulated at day 0 and subsequently upregulated; together with CYP94C1, these changes may attenuate jasmonate-associated defense signaling. For cell remodeling and defense coordination, ABT reduced the expression of genes associated with cell-wall rigidity while inducing EXPA11 (expansin) at day 20, potentially facilitating root primordium emergence. Meanwhile, PR-1 (pathogenesis-related protein 1) was transiently upregulated at days 0, 20, and 30, and the concomitant modulation of WRKY transcription factors and RPM1 suggests enhanced defense readiness. Integrative network analysis further indicated that a GH3–ERF1/2–PR-1 module links hormonal and defense cues and may activate BAT1 (energy metabolism) and RBOHB (ROS production) to support adventitious root elongation. Collectively, these results suggest that ABT improves rooting efficiency by reshaping hormonal homeostasis and coordinating cell-wall reconstruction with a pre-activated defense state, thereby providing a conceptual framework for balancing root induction and defense responses during vegetative propagation in forest trees. Full article

Background: House dust mites (HDM) are one of the significant indoor allergen sources which cause IgE-mediated responses in most of the allergic individuals. HDMs are found in human habitats worldwide and Der p 2 is one of the major clinically relevant HDM allergens involved in triggering allergic diseases. The recombinant production of Der p 2 in plant systems provides a cost-effective and viable platform for developing diagnostic kits and allergen-specific immunotherapy. Methods: The D. pteronyssinus Der p 2 allergen was transiently expressed in Nicotiana benthamiana and its immunogenicity was evaluated in mice. The Der p 2 coding sequence was cloned into a geminiviral plant expression vector and introduced into N. benthamiana leaves via Agrobacterium tumefaciens-mediated infiltration. Recombinant Der p 2 proteins were purified from the crude extracts and confirmed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis and Western blot. The immunogenicity of the plant-produced Der p 2 proteins was further evaluated by immunizing mice following a prime–boost immunization regimen, and Der p 2-specific antibody responses were assessed by ELISA. Results: Recombinant Der p 2 was successfully expressed and purified from N. benthamiana, and immunized mice developed high levels of Der p 2-specific IgG antibodies, with antibody titers increased after booster immunization. Conclusions: The results demonstrate that the transient expression of Der p 2 in plants is a feasible and effective strategy for producing immunologically active recombinant allergen proteins for diagnostic and potential clinical applications. Full article

Bone metastasis is a devastating complication of advanced osteotropic malignancies, notably breast, prostate, lung carcinomas, and malignant melanoma, and remains a primary driver of mortality. Historical paradigms have conceptualized skeletal dissemination almost exclusively as a hematogenous process wherein circulating tumor cells colonize receptive bone marrow niches. However, this model fails to reconcile why lymph node metastasis consistently serves as a potent predictor of bone involvement even though therapeutic lymphadenectomy rarely prevents distant spread. This discordance suggests that lymph nodes function not merely as passive reservoirs but as active ‘evolutionary gateways’ that sculpt bone-tropic metastatic clones. In this review, we introduce the Lymphatic–Bone Axis, a framework integrating lymphatic biology into models of bone metastasis. We synthesize emerging evidence elucidating how the lymph node microenvironment primes tumor cells through CCR7-CXCR4 switching, induction of osteomimicry programs, and metabolic reprogramming that favors survival within the bone marrow. We also discuss preclinical data demonstrating direct intranodal intravasation via high endothelial venules (HEVs), providing a rapid route into the systemic circulation that bypasses the thoracic duct. Beyond consolidating current knowledge, we outline a research agenda for dissecting this axis, including longitudinal single-cell transcriptomic mapping and functional assessments of lymph node-derived tumor cells. Finally, we consider translational implications, highlighting why bone-targeted agents alone may prove insufficient once cells are conditioned within lymphatic niches. By mechanistically linking lymphatic priming to skeletal colonization, this review informs the rational design of multimodal therapeutic approaches that jointly target lymphatic transit and the bone microenvironment. Full article

Genome editing has emerged as a transformative approach for understanding and treating retinal degenerative diseases. Combining this technology with pluripotent stem cells provides an ideal platform for modeling human development and disease, and investigating emerging therapeutic strategies ultimately aimed towards in vivo correction. This approach enables both functional studies to understand retinal degeneration and the early development of targeted therapies for inherited disease. This review offers a comprehensive overview of genome-editing techniques and the ability to create new clinically relevant models to understand human disease in retinal research, focusing on the use of the CRISPR-Cas9 system in induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), as well as highlighting recent advancements in base and prime editing. Gene editing in various retinal diseases is discussed in context of studies focusing on disease modeling or developing therapeutic strategies. Continued refinement of these techniques will be essential for advancing translational applications in retinal disease treatment. Full article

The carob tree (Ceratonia siliqua L.) is indigenous to the Mediterranean basin, noted for its adaptability to biotic and abiotic stresses and its long history of use in traditional agroforestry systems. This review critically analyzes the phytochemical composition of carob, its traditional medicinal uses, and its contemporary applications in the cosmetic, pharmaceutical, and agri-food sectors. Particular attention is placed on the valorization of carob pods, seeds, and leaves, which are transformed into high-value products, including locust bean gum and polyphenol-rich extracts. Recent studies indicate that carob is a rich source of bioactive compounds, particularly phenolic acids and flavonoids such as gallic acid, chlorogenic acid, ellagic acid, catechins, quercetin, and luteolin. These compounds have primarily been investigated in vitro and in vivo, where they exhibited antioxidant, antimicrobial, and potential cardioprotective and gastrointestinal-related effects. This chemical diversity underscores their potential as a prime substitute for future nutraceutical and pharmaceutical applications. The review further addresses the ecological and socio-economic relevance of carob cultivation, particularly in countries such as Algeria, where reforestation and agro-industrial valorization remain underexploited despite their significant economic potential. Overall, this work highlights the need for a comprehensive and critical evaluation of carob-derived bioactive compounds and encourages further well-designed studies, especially clinical investigations, to better substantiate their health-related benefits while supporting sustainable use of this multipurpose species. Full article

Modern agriculture is undergoing a paradigm shift toward eco-friendly methodologies that enhance seed material quality while minimizing chemical inputs. This study evaluates the impact of Effective Microorganism (EM) exposure (variants E1 and E2) on the morpho-physiological parameters and phytosanitary health of potato tubers. The primary objective was to determine the efficacy of microbial priming in suppressing the infection rates of Streptomyces scabies (common scab) and Rhizoctonia solani (black scurf) across 14 genetically diverse cultivars. A three-year field experiment (2019–2021) was conducted using a split-plot design with three replications. The study analyzed the interaction between EM exposure times and the genetic resistance potential of the selected cultivars. Statistical analysis confirmed that pre-planting microbial treatments significantly inhibited pathogen development. EM applications (E1 and E2) reduced the infection rates of both S. scabies and R. solani through an “escape mechanism,” whereby treated tubers exhibited accelerated biomass accumulation and reached physiological maturity before peak pathogen pressure. Furthermore, treatments optimized the physiological state and vigor of the tubers, establishing a robust physiological barrier against soil-borne infections. The application of EMs proves to be a highly effective, non-invasive biostimulation method. A significant difference was observed in the responding varieties between EM treatments and the cultivars innate genetic resistance, particularly in cultivars with higher baseline resistance. The use of EM biostimulants significantly modifies the health of tubers, and the direction of these changes is strictly determined by the variety factors. The results suggest that microbial priming not only enhances plant growth kinetics but also induces systemic resistance, offering a viable ecological alternative to traditional chemical seed dressings in sustainable potato production. Full article

Plant defence elicitors have emerged as pivotal components of sustainable fruit crop protection, aligning with One Health principles by reducing chemical residues while enhancing ecosystem and human health. These exogenous agents—ranging from phytohormones, peptides, and cell-wall fragments to botanical extracts—activate or prime innate immune responses in fruit crops through pattern-triggered immunity (PTI), systemic acquired resistance (SAR), and induced systemic resistance (ISR) pathways. Over the last decade, advances in receptor biochemistry, genomics, metabolomics, and epigenetics have transformed this field. Recent mechanistic advances reveal that oligosaccharide elicitors derived from chitosan and laminarin are perceived by membrane-localised pattern recognition receptors (PRRs) that confer broad-spectrum resistance against fungal, bacterial, and viral pathogens in fruits. By contrast, no specific protein receptor has been identified for harpin proteins, the emerging evidence indicating that harpin perception may occur through direct interaction with plasma-membrane lipids or lipid-associated proteins. The One Health approach is supported by elicitors, biodegradability, minimal environmental persistence, and the ability to reduce synthetic fungicide usage by 30–70%. However, challenges remain regarding batch-to-batch variability, sensory acceptance due to bitter compounds, regulatory hurdles for novel food approvals, and the need for optimised application protocols that consider the fruit genotype and developmental stage. The future integration of nanotechnology for targeted delivery, the artificial-intelligence-driven screening of active molecules, and synergistic combinations with biocontrol agents promises to overcome these limitations, positioning plant defence elicitors as cornerstone tools for resilient, health-promoting fruit production systems. Full article

This essay offers a philosophical and bioethical upholding of Dignitas Personae §27, which cautions against the use of human gene editing (HGE) for non-therapeutic purposes. After situating the debate within the historical development of gene-editing technologies, the essay classifies enhancement-oriented interventions—physical, behavioral, and cognitive—and argues that such practices risk violating human dignity, diminishing authentic freedom, and promoting a deterministic anthropology. Drawing on a personalist framework, the analysis incorporates insights from neuroscience, genetics, and natural law. In the second part, the essay examines Aristotelian–Thomistic metaphysics, integrating Ernest Mayr’s notion of teleonomy to explain how the rational soul actualizes its perfect operations. It is argued that non-therapeutic HGE, especially germline modifications, may disrupt the ontological structure of the human person by impairing the soul’s expression through properly disposed prime matter. Ultimately, Dignitas Personae stands as a coherent and prescient response to emerging biotechnologies, defending the human person against technocratic reductionism and the ideological drive to transcend our embodied finitude. Full article

Pigeon Newcastle disease poses a persistent threat to the global pigeon industry, underscoring the need for effective vaccination strategies. While both inactivated and DNA vaccines offer distinct advantages, the immunogenicity of a combined heterologous regimen remains underexplored. This study evaluated and compared three immunization strategies in pigeons: a DNA vaccine encoding the NDV F protein fused with chicken IL-18, an inactivated vaccine from a local virulent strain, and a DNA prime-inactivated boost regimen. The preparation workflows for both vaccine platforms are described in detail to provide methodological context for the immunological comparison. Critically, the prime–boost regimen elicited significantly higher hemagglutination inhibition (HI) antibody titers than either vaccine administered alone, demonstrating a clear synergistic effect. These findings highlight the complementary roles of the two platforms and provide a strong immunological rationale for further evaluation of this sequential strategy. Future studies incorporating viral challenge experiments and long-term immune monitoring are needed to determine whether the enhanced HI antibody response translates into protective efficacy under field conditions. Full article

Pear scab, caused by Venturia pyrina, poses a threat to pear cultivation, with particularly severe consequences for Portugal’s high-value Rocha pear industry. Despite its economic impact, few biological control agents are currently available. In this work, the phenotypic and genomic characterization of Pseudomonas capeferrum NFX1 is performed and its role as an effective biocontrol agent against V. pyrina is reported. Detailed genomic analysis revealed that strain NFX1 and other members of the Pseudomonas capeferrum species contain key biosynthetic gene clusters involved in pathogen antagonism, including the cyclic lipopeptide putisolvin. Phenotypic assays showed that strain NFX1 significantly inhibited V. pyrina growth, spore germination, and reduced pear scab lesion severity and fungal colonization in detached leaf assays. Moreover, strain NFX1 reprogrammed the Rocha pear leaf transcriptome to be consistent with a priming state and induced systemic resistance. A novel image-based method quantifying lesion darkening as a proxy for pear scab severity in detached leaves and a qPCR assay targeting the V. pyrina ef1-α gene and optimized for fungal DNA detection in infected pear leaves were also developed, thereby establishing a laboratory workflow specifically tailored to biocontrol evaluation against V. pyrina. Ultimately, the obtained results demonstrated the potential of P. capeferrum NFX1 for sustainable pear scab control. Full article

Abiotic stresses severely constrain the growth, yield, and quality of horticultural plants, collectively posing major challenges to sustainable production under changing climatic conditions. Nitric oxide (NO) is a key signaling molecule that modulates plant responses to abiotic stress by integrating with redox regulation systems, hormonal crosstalk pathways, ion homeostasis mechanisms, and transcriptional control networks. Rather than functioning as an isolated regulator, NO participates in dynamic signaling frameworks whose outcomes depend on concentration, timing, cellular redox status, and interaction with other signaling molecules. This review synthesizes current knowledge on NO-mediated mechanisms contributing to abiotic stress tolerance and examines their relevance to sustainable horticultural crop management. After outlining the historical recognition of NO as a plant signaling molecule, we discuss stress-responsive NO-dependent processes, including S-nitrosylation-based post-translational modification, NO–reactive oxygen species (ROS) interactions, and the modulation of stress-responsive transcriptional programs. The roles of NO in tolerance to drought, salinity, extreme temperature, and heavy metal stress are analyzed with emphasis on experimentally supported physiological and molecular responses. We further evaluate evidence from fruit, vegetable, ornamental, and medicinal crops, highlighting how NO-associated signaling correlates with yield stability, quality-related traits, and post-harvest performance under stress conditions. Finally, NO-based strategies such as priming, donor application, and integration with biostimulants are critically assessed in the context of climate-resilient and sustainable horticulture, with attention to translational constraints and field-level feasibility. By connecting mechanistic insights with applied considerations, this review provides a structured framework for evaluating the potential and limitations of NO-based approaches in abiotic stress management of horticultural crops. Full article

Abiotic stresses disrupt redox homeostasis and reduce crop productivity. Antioxidant networks support resilience by limiting excess reactive oxygen species (ROS) and maintaining redox signalling for stress perception, gene expression, and metabolic reprogramming. We summarize advances (2000–2025) in ROS generation, detoxification mechanisms, and signalling across organelles, including chloroplasts, mitochondria, peroxisomes, and the apoplast. This includes compartmentalized enzymes—superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione peroxidase (GPX), and glutathione reductase (GR)—as well as the peroxiredoxin–thioredoxin system and non-enzymatic buffers like ascorbate, glutathione, tocopherols, carotenoids, and flavonoids. We uniquely synthesize these findings in a compartment-resolved “redox rheostat” model, linking ROS concentration–time windows (signaling vs. damage) to antioxidant network design (kinetic tiers, compartmentation, and trade-offs) and identifying intervention points for breeding, genome editing, and field-scale priming. We emphasize constraints, such as NADPH supply and antioxidant recycling capacity, that lead to context-dependent outcomes. We evaluate omics, transgenic strategies, genome editing (CRISPR and Cas systems), exogenous applications, and plant–microbe associations. This synthesis clarifies how antioxidant systems protect photosynthetic and respiratory machinery while supporting signalling, thus outlining routes to climate-resilient, yield-stable crops across varied environments and stresses. Full article

Background/Objectives: Epidemiological studies have proven that coxsackievirus B3 (CVB3) is the major virus that causes acute and chronic myocarditis and pancreatitis. Currently, there are no antiviral therapeutic drugs or vaccines that are available for use as clinical therapeutics or vaccines. Subunit polypeptides-based vaccines, especially when combined with adjuvants, represent safe and effective vaccine platforms because they are considered to be better immunogens. The viral capsid protein VP1 of CVB3 is the most immunogenic viral polypeptide, providing opportunities for its use in designing subunit polypeptide vaccines. In the present study, we designed and produced a CVB3 vaccine candidate based on the recombinant expression of the major immunogenic viral protein VP1 of a wild-type CVB3 strain. Methods: We assessed its induced humoral and cellular immune responses and then evaluated its protective immunity against pathogenic CVB3 strain challenges in a Balb/c mouse model. Neutralizing specific antibodies and cytokine interferon gamma (INF-γ) production were determined in the sera of both prime- and prime-boost-immunized mice with the vaccine candidate. Results: Our results demonstrate that the recombinant rVP1 expressed in a eukaryotic insect cell baculovirus vector system elicited cellular and humoral immune responses, protecting Balb/c mice from lethal challenges. Conclusions: Hence, the vaccine produced based on the recombinant expression of VP1 is a promising and potential candidate against natural CVB3 infections. Full article

Radiation exposure from environmental sources, medical procedures, or space exploration poses considerable risks to human health, with profound effects on immune function and inflammatory responses. Radiotherapy (RT) is a cornerstone of modern cancer treatment, leveraging ionizing radiation to induce DNA damage and tumor cell death. However, its biological effects extend beyond direct cytotoxicity, exerting complex and context-dependent influences on both innate and adaptive immunity. Ionizing radiation can enhance antitumor immune responses by promoting tumor antigen release, activating dendritic cells, and augmenting cytotoxic T-cell priming. Conversely, it can also induce immunosuppressive mechanisms, including lymphocyte depletion, regulatory T-cell expansion, immune checkpoint upregulation, and chronic inflammatory signaling, which may limit therapeutic efficacy. These immune effects are critical for optimizing RT protocols, particularly in the era of immunotherapy, where immune modulation plays a pivotal role in treatment efficacy. This review summarizes the current knowledge concerning how radiation induces immune and inflammatory responses in cells and tissues; focuses on key molecular pathways such as the DNA damage response, cGAS–STING signaling, and immune checkpoint modulation; and discusses their clinical implications. These findings provide potential therapeutic strategies for cancer treatment by harnessing the immunomodulatory potential of radiation while reducing adverse effects and for the prevention and treatment of radiation-related diseases. Full article