Search Results (5,135)

Metastasis, the primary cause of cancer mortality, relies on malignant cells acquiring extreme mobility and mechanical plasticity. We posit that this physical transition is driven not by de novo genetic innovations but by an atavistic reversion to highly conserved cytoskeletal blueprints, termed “Fungal Islands.” Through in silico sequence alignments and molecular docking, we investigated structural homology between human septin-9 (SEPT9) and its yeast ortholog, Cdc3. Our analysis reveals structural and thermodynamic parity within the G1/P-loop catalytic core across billions of years of eukaryotic divergence. This precise preservation of spatial configuration provides strong evidence against convergent evolution, demonstrating the core septin engine is constrained by intense purifying selection. Consequently, we argue that malignant cells exapt these functionally immutable ancestral nodes to drive a biomechanical shift, mirroring the invasive mechanics of fungal hyphal tips. This identifies a non-mutating structural template for next-generation ‘migrastatic’ therapies, offering a strategy to disable cancer’s migratory machinery while evading the mutational resistance typical of modern kinase inhibitors. Full article

Endothelial dysfunction is an early event in the development of cardiovascular diseases and is characterized by impaired barrier function, inflammatory activation of endothelial cells (ECs), and alterations in lipid metabolism. In addition to typical (mononuclear) endothelial cells (TECs), multinucleated variant endothelial cells (MVECs) are present within the vascular wall; however, their functional role remains poorly understood. The aim of the present study was to investigate the molecular and functional characteristics of MVECs and their potential contribution to the development of endothelial dysfunction. Primary human umbilical vein endothelial cells (HUVECs) were used, and multinucleated cells were generated by polyethylene glycol-induced fusion. Cells were incubated under control conditions or exposed to low-density lipoproteins (LDL; 100 µg/mL, 24 h). A comprehensive analysis was performed, including transcriptomic and proteomic (secretome) profiling using gene set enrichment analysis (GSEA), as well as functional assays assessing transendothelial LDL transport, intracellular cholesterol accumulation, macrophage migration, and the expression and secretion of pro-inflammatory cytokines (IL-6, IL-8). MVECs exhibited pronounced differences compared to TECs. GSEA revealed reduced enrichment of pathways related to canonical nuclear factor kappa B (NF-κB) signaling and negative regulation of NF-κB transcription factor activity, actin cytoskeleton organization, focal adhesion assembly, basement membrane organization, and vesicle-mediated transport in MVECs relative to TECs, indicating impaired cytoskeletal integrity, altered cell–matrix interactions, dysregulated inflammatory signaling, and reduced vesicular trafficking activity. Functionally, MVECs demonstrated an increased capacity for cholesterol accumulation and enhanced transendothelial migration of macrophages. Notably, transendothelial LDL transport across the MVEC monolayer was not increased, suggesting a predominance of intracellular lipid accumulation. MVECs also exhibited a pronounced pro-inflammatory phenotype, characterized by elevated expression and secretion of IL-6 and IL-8. Taken together, these findings indicate that MVECs represent a functionally altered endothelial phenotype with impaired barrier function, dysregulated lipid metabolism, and enhanced inflammatory activity. Local accumulation of MVECs within the vascular wall may contribute to the formation of pro-atherogenic regions and play a role in the initiation and progression of endothelial dysfunction. Full article

Objective: To report a rare case of bilateral iris metastasis from small cell lung carcinoma (SCLC) and systematically review the literature on SCLC-associated iris metastases, with emphasis on clinical presentation, management, and outcomes. Materials and Methods: A systematic literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, ScienceDirect, Scopus, and Web of Science were comprehensively searched on 10 July 2025. Eligible studies included English-language reports of iris metastasis originating from SCLC in human subjects. Case report: A 58-year-old woman with previously treated SCLC developed bilateral iris metastases one year after complete remission of the primary tumor. Ophthalmic examination revealed whitish-gray, vascularized iris masses with iridocorneal angle involvement, associated with secondary angle-closure glaucoma and markedly elevated intraocular pressure (48 mm Hg) in the left eye. Cyclocryotherapy, preceded by systemic and topical antiglaucoma therapy, resulted in pain relief and a reduction in intraocular pressure; the patient died four months later due to pneumonia. Results (Systematic Review): Seventeen studies comprising 17 patients were included; the median age was 60 years, and 64.7% were male. The median interval from SCLC diagnosis to ocular presentation was 4 months, although iris metastasis was occasionally the initial or concurrent manifestation of disease. The most common presenting features were visual impairment (58.8%), ocular pain (41.2%), and elevated intraocular pressure (41.2%), while iris neovascularization (35.3%) and synechiae (29.4%) were also frequent. Bilateral involvement was reported in only one previous case. Treatment approaches were heterogeneous and included antiglaucoma therapy, systemic chemotherapy, local radiotherapy, anti-VEGF therapy, and enucleation. Among patients with available follow-up (n = 12), 58.3% died within a median follow-up of 7.5 months. Conclusions: Bilateral iris metastasis from SCLC is rare and may occur as a manifestation of recurrent disease after remission. It is an aggressive condition characterized by nonspecific ocular symptoms, variable management, and poor survival, underscoring the importance of early recognition and the need for evidence-based diagnostic and therapeutic strategies. Full article

Background: The metastatic dissemination of melanoma involves adhesion of circulating tumor cells within organ-specific vascular beds; however, the relative contribution of the endothelial environment versus that of the melanoma-intrinsic molecular state remains unclear. Materials and Methods: We quantified the in vitro adhesion of primary (n = 5) and metastatic (n = 3) melanoma cell lines to human hepatic, brain, and pulmonary endothelial cells under co-culture conditions, and we profiled the expression of 86 adhesion- and extracellular-matrix-related genes in melanoma and endothelial cells. Results: Adhesion was highest for the hepatic endothelium, intermediate for the pulmonary endothelium, and lowest for the brain endothelium. This endothelial preference was conserved in both primary and metastatic melanoma cells, though metastatic cells exhibited higher absolute adhesion. The linear mixed-effect models revealed that the effects of adhesion state on melanoma gene expression were modest and varied by endothelial type, whereas melanoma origin had more widespread and larger effects (mean absolute standardized coefficients of 0.32–0.47 versus 0.60–0.87, respectively). The expression of three genes (SPP1, ITGA11, and MMP2) was associated with melanoma origin in all endothelial types. Spearman’s co-expression analysis revealed endothelial-type-specific gene networks, and within-sample permutation confirmed the non-random coordination in all three endothelial types. Conclusions: Our findings support a model in which endothelial organ specificity contributes to melanoma cell adhesion behavior and associated transcriptional patterns, highlighting the importance of the vascular interface as a biologically active mediator of early metastatic cell–endothelium interactions. Full article

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

Multiple sclerosis is an immune-driven neurological disease that affects myelinated axons in the central nervous system. However, the trigger of the (dysregulated) immune reactions is not known. According to Wilkin’s primary lesion theory, myelin-reactive T cells present in the immune repertoire hyper-react to myelin antigens that are released from idiopathic lesions within the central nervous system. However, neither the cause of the primary lesion nor the cause of the immune hyper-reactivity is known. We investigated whether these unknown activation signals may be relayed by common herpesviruses. In this concept paper, we propose the novel paradigm that the trigger of autoimmunity in MS comprises a conspiracy of three common herpesviruses: human herpesvirus-6A as a potential trigger of primary lesions due to its proven capacity to cause oligodendrogliopathy, cytomegalovirus as a trigger for the formation of effector memory cytotoxic T cells with proven capacity to induce multiple sclerosis pathology in a non-human primate MS model and Epstein-Barr Virus due to its capacity to render B cells capable to effectively present a critical myelin antigen to these effector memory cytotoxic T cells. Full article

Background: Chlorella, a unicellular green alga, is currently one of the most popular algae supplements due to its high content of bioactive compounds. Chlorella’s wide range of macro- and micronutrients, including chlorophyll compounds and carotenoids, has been suggested to influence various disorders related to the digestive and nervous systems. This review’s primary purpose was to critically analyze the effects of Chlorella intake on gut microbiota and brain function. Methods: The authors conducted a systematic review with narrative synthesis of peer-reviewed articles written in English and published in PubMed, Web of Science, and Scopus spanning the years 2009 to 2026 (PROSPERO registration number CRD42024527705). The search protocol was performed following PRISMA guidelines. Primary outcomes encompassed physiological variables, such as gut microbial composition, short-chain fatty acids, brain-derived neurotrophic factor, and hippocampal cell density. Secondary outcomes were assessed through neurobehavioral tests and psychological questionnaires. Results: Out of the 1333 articles identified, 47 studies were deemed eligible, and 21 met the predefined criteria, subsequently incorporated into this systematic review. In total, 10 articles documented interventions involving Chlorella and their effects on the gut microbiota, whereas 11 articles investigated several variables pertinent to brain function. Most of the studies included were conducted in animal models, with only a limited number of human trials. Nineteen studies (90%), predominantly preclinical, reported positive associations between Chlorella consumption, gut microbiota modulation, and physiological or neurobehavioral markers related to the gut–brain axis. Conclusions: Chlorella consumption may modulate gut microbiota composition and function, potentially influencing brain-related processes. However, the available literature lacks studies simultaneously addressing both gut microbiota and brain health parameters limiting the understanding of the underlying physiological mechanisms. Full article

Osteoporosis (OP) is a complex disease in which several immune-related genes have been identified as contributing to susceptibility and disease progression. Despite efforts to achieve functional validation, many of these genes, such as interferon-gamma (IFNG), remain the subject of unresolved mechanisms. The present study aimed to examine whether the IFNG -1616 (G>A, rs2069705) polymorphism was associated with postmenopausal OP. A total of 251 OP patients and 115 healthy controls were genotyped to assess the association between the IFNG -1616 (G>A, rs2069705) polymorphism and osteoporosis. To further investigate the biological role of IFN-γ in bone metabolism, human SaOs-2 osteosarcoma cells were treated with recombinant IFN-γ (2 and 100 U/mL), and calcification and cell viability were evaluated using Alizarin Red staining and the MTT assay, respectively. We found that the IFNG rs2069705 G allele was associated with an increased risk of OP (OR = 1.45, 95% CI = 1.03–2.05, p = 0.03). Furthermore, serum IFN-γ levels did not differ significantly between genotype groups. In SaOs-2 cells, IFN-γ (2 U/mL) significantly increased viability (p = 0.017) and enhanced calcification in a dose-dependent manner. The IFNG rs2069705 G allele may confer susceptibility to postmenopausal OP. IFN-γ promotes osteoblast viability and mineralization at low concentrations, suggesting a potential anabolic role that warrants further investigation in human primary osteoblasts. Full article

The valorization of culinary by-products into functional bioactive resources represents a significant advancement in sustainable biotechnology. This study characterizes an extract derived from “battuto toscano” by-products, a traditional blend of garlic, onion, carrot, and celery trimmings, recovered through circular economy principles. Comprehensive antioxidant profiling was performed alongside biological evaluations on human cell lines and anti-glycation assays. Results from Folin–Ciocalteu, FRAP, and TEAC assays confirmed a high concentration of secondary metabolites with significant scavenging capacity. In vitro testing on primary human fibroblasts and HaCaT keratinocytes revealed a concentration- and time-dependent biological response, with lower concentrations showing better compatibility and transiently enhancing HaCaT metabolic activity. Furthermore, BTE reduced AGE-associated fluorescence in the BSA–glucose model, particularly at 5 mg/mL, supporting its potential anti-glycation activity. These findings establish “battuto toscano” by-products as a reservoir of sustainable biomolecules. This study offers a transformative resource for the pharma/nutraceutical sectors by bridging culinary tradition with biomedical innovation. Full article

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as liraglutide (LIR), are widely used in humans to treat type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease. In mammals, GLP-1 RAs have been shown to influence hepatic lipid metabolism, although the underlying mechanisms remain unclear. In fish, GLP-1 also plays an important role in regulating hepatic processes, including glycogenolysis, gluconeogenesis, and lipolysis. However, the effects of GLP-1 RAs on liver lipid metabolism in fish remain largely unexplored. Objective: This study aimed to evaluate the effects of LIR on lipid target genes using primary hepatocytes from brown trout as an in vitro model. Methodology: After 24 h, a hepatocyte monolayer culture was established, and cells were exposed for 24 and 48 h to supplemented L-15 medium (control), 0.1% dimethyl sulfoxide in supplemented L-15 medium (solvent control), and five single exposures to LIR at 1, 10, 100, 500, and 1000 nM. After 24 and 48 h, cell viability was assessed using the trypan blue exclusion assay. Gene expression was analysed by real-time qPCR, targeting genes involved in lipogenesis, lipid transport, and cholesterol efflux. Results: No concentration-dependent effects on cell viability were observed. Gene expression analysis showed that LIR exposure modulated the mRNA levels of lipid-related genes, including acetyl-CoA carboxylase (ACC), acyl-CoA long-chain synthetase 1 (Acsl1), and fatty acid synthase (FAS), with time being the main influencing factor. Overall, expression levels were higher at 48 h compared to 24 h. Additionally, dose-dependent effects were observed for ACC expression, with higher LIR concentrations showing significant differences compared to controls. Conclusions: These findings indicate that LIR modulates lipid-related gene expression in primary hepatocytes of brown trout without affecting cell viability. The results suggest that GLP-1 receptor activation may influence key pathways involved in hepatic lipid metabolism, with time-dependent effects playing a predominant role. Overall, this study supports the use of brown trout primary hepatocytes as a suitable in vitro model for investigating hepatic lipid responses to LIR and other GLP-1 receptor agonists, while providing initial insight into their potential effects in fish. Full article

Background: Toxoplasmosis is a prevalent zoonotic disease worldwide, affecting approximately one-third of the global human population. Primary infection with Toxoplasma gondii during pregnancy can induce miscarriage or congenital infection, leading to irreversible damage to the foetus. Moreover, reactivation of T. gondii infection in immunosuppressed individuals can result in fatal outcomes. No vaccine exists to prevent human disease caused by this parasite. Thus, a vaccine that could induce complete and lasting protection against human toxoplasmosis is an unmet need. Method: In this work, BALB/cByJ mice were intranasally immunised with a subunit vaccine consisting of T. gondii membrane proteins (TGMP) from the T. gondii Me49 strain plus CpG-oligodeoxynucleotide adjuvant (CpG). Antibody responses were analysed by ELISA, while T-cell responses were evaluated by flow cytometry. The immunogenic proteins present in TGMP were identified by mass spectrometry, and parasite burden was quantified by qPCR. Result: The results showed raised TGMP-specific serum IgG and intestinal IgA antibody levels, and parasite-specific IFN-γ-producing CD4⁺ and CD8⁺ memory T cells. Dense granule proteins (GRA) 2 and 7, surface antigen (SAG)-related sequences 25, 29B, and 34A, microneme protein (MIC) 10, toxofilin, nascent polypeptide-associated complex (NAC) domain-containing protein, and NAC subunit beta were identified as immunogenic proteins. Mice immunised with TGMP+CpG were challenged with T. gondii tachyzoites and showed a significant reduction in the parasitic burden in the peritoneal exudate, spleen, and lungs, compared to mice sham-immunised with CpG alone. Conclusions: Altogether, these results indicate that mucosal immunisation with TGMP plus CpG adjuvant is worth exploring as a vaccination approach to prevent toxoplasmosis. Full article

In recent years, the touch panel industry has experienced rapid growth. With technological maturation and progressive cost reduction, touch technology has been widely adopted in human–machine interfaces. Currently, touch panels are predominantly employed in smartphones and tablet devices, and the industry is increasingly pursuing thinner, lighter designs, driving the development of diverse touch technologies, including one-glass solution (OGS), on-cell, and in-cell architectures. To enhance competitive advantage within the touch panel industry, it is essential to improve production efficiency and elevate product quality; consequently, yield has become a critical metric for evaluating industrial competitiveness. This study adopts the electrical test yield of Touch-on-Lens (TOL) touch-sensing glass as the primary performance indicator. A Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) framework is applied to systematically address impedance-related quality defects occurring during manufacturing. First, key quality characteristics (KQCs) of the TOL touch-sensing glass process are rigorously defined. Subsequently, measurement system analysis (MSA) and process capability assessment are conducted. Next, the Taguchi method is employed to identify the most influential process factors affecting electrical test yield. Finally, response surface methodology (RSM) is utilized to determine the optimal combination of process parameter settings that maximize electrical test yield. Results from the empirical case study demonstrate that the electrical test yield improved significantly—from 90.2% to 93.6%. This outcome validates that the integrated application of the Six Sigma DMAIC methodology, combined with the Taguchi method and RSM, effectively enhances the electrical test yield of TOL sensing glass. The proposed approach offers a robust, data-driven improvement framework applicable to touch panel manufacturers seeking to optimize sensing-glass fabrication processes—thereby supporting broader industry efforts to improve product quality and reduce manufacturing costs. Full article

Leukocyte recruitment from blood into tissues involves sequential adhesive steps, including rolling and integrin-dependent arrest. VLA-4 can support firm adhesion and, in some settings, rolling interactions, whereas CD44–hyaluronan interactions have also been implicated in leukocyte rolling. Here, we used adhesion assays and parallel-plate flow chamber experiments to analyze CD44–hyaluronan-dependent monocyte interactions on ECV304 monolayers and to compare them with α4-integrin-sensitive adhesion on endothelial monolayers. WEHI 78/24 monocytoid cells interacted with ECV304 monolayers in a CD44- and hyaluronan-dependent manner, whereas adhesion to HMEC-1 and bEnd.3 monolayers was sensitive to α4-integrin blockade. Blocking CD44, adding soluble hyaluronan, or treating ECV304 monolayers with hyaluronidase reduced adhesion and rolling. Mixed primary human monocyte preparations also showed CD44-dependent adhesion and rolling on ECV304 monolayers. ECV304 cells are interpreted here not as endothelial cells, but as T24-derived, hyaluronidase-sensitive cellular monolayers useful for functional analysis of CD44–hyaluronan-dependent interactions. These findings support a substrate-dependent functional hierarchy in which CD44–hyaluronan-dependent monocyte rolling becomes detectable when α4-integrin-dependent adhesion is not dominant, while emphasizing the cell-model-based nature of the assay. Full article

In recent years, bisphenol F (BPF) and bisphenol S (BPS) have been used in several everyday products to replace bisphenol A (BPA), since exposure to BPA has been associated with the development of several pathologies. However, recent studies have also been associating exposure to BPA substitutes with the development of various pathologies, including cardiovascular diseases, and the safety of BPA substitutes for human health has been questioned. Thus, this study aimed to investigate and compare BPA, BPF and BPS effects on arterial tone and to explore the mechanisms involved. The results suggest that BPA, BPS and BPF exert non-genomic and endothelium-independent relaxant effects on arteries and smooth muscle cells from the umbilical cord. Regarding genomic effects, the results suggest that BPA, BPF, and BPS disrupted the primary mechanisms underlying HUA relaxation by interfering with the cGMP signaling pathway and modulating the Ca²⁺ channels activity. Moreover, these results suggest that BPF alters the vasorelaxant response more than BPA and BPS. Therefore, replacing BPA with its substitutes does not appear to be beneficial for human cardiovascular health. Thus, in the future, the vascular effects of these bisphenols should be further evaluated to clarify their modes of action and future implications for maternal-fetal health. Full article

Background/Objectives: Chlamydia trachomatis (CT) is a prevalent sexually transmitted pathogen associated with pelvic inflammatory disease, infertility, and has been proposed as a potential contributor to carcinogenesis through chronic inflammation and tissue remodeling. The molecular mechanisms triggered by CT infection in fallopian tube cellular contexts and their relevance to ovarian cancer transcriptomes remain incompletely understood. Methods: We analyzed GSE109428, profiling primary human fallopian tube mesenchymal cells infected with CT, to identify differentially expressed genes and characterize affected pathways using g:Profiler and STRING protein–protein association networks (confidence ≥ 0.7). To provide translational context, we computed ssGSEA scores in TCGA-OV for four signatures capturing IFN/ISG, TNF/NF-κB, NOD/innate immunity, and ECM programs, and evaluated inter-signature correlations and exploratory associations with overall survival (OS) and progression-free interval (PFI). Results: CT infection induced sustained inflammatory and interferon-associated transcriptional programs, with STRING networks highlighting cytokine hubs and a densely connected ISG module. Genes downregulated at 48 h post-infection (48-hpi) showed coherent enrichment for ECM organization and adhesion pathways. In TCGA-OV (n = 307), inflammatory and innate immune signatures co-occurred across tumors, with moderate correlations between TNF/NF-κB and NOD/innate (ρ = 0.591) and IFN/ISG and NOD/innate (ρ = 0.534). Exploratory survival analyses showed no significant associations with OS or PFI in Kaplan–Meier analyses or multivariable Cox models, including clinically adjusted and tumor microenvironment-adjusted specifications. Conclusions: CT infection induces sustained inflammatory and interferon-linked programs and coordinated repression of ECM networks in fallopian tube mesenchymal cells. Analogous immune transcriptional states co-occur in ovarian tumors, though the signatures evaluated did not yield robust prognostic signals in TCGA-OV. As this is an entirely in silico study without experimental validation, these findings should be treated as hypothesis-generating; thus, further mechanistic and experimental studies are warranted to clarify how CT infection-associated pathways may intersect with female tumorigenesis. Full article