Search Results (35,711)

Fusobacterium nucleatum (F. nucleatum) is a key periodontal pathobiont associated with oral inflammation. This bacterium forms biofilms and expresses adhesins that facilitate its adhesion to and invasion of gingival epithelial cells. These processes disrupt the epithelial barrier and trigger oral inflammation, and in some cases, systemic inflammation. Conventional antimicrobial strategies predominantly depend on the utilization of antibiotics. Nevertheless, this can result in the proliferation of drug-resistant strains and the disruption of the oral microbiome equilibrium. As the predominant human milk oligosaccharide, 2′-Fucosyllactose (2′-FL) demonstrates considerable promise in inhibiting pathogenic bacterial adhesion and fortifying epithelial barrier function, mediated by its characteristic structural and bioactive attributes. In this study, we showed that 2′-FL attenuates the expression of virulence genes in F. nucleatum, reduces biofilm formation, and suppresses the bacterium’s ability to adhere to human gingival epithelial cells (HGECs). Furthermore, at the transcriptional level, 2′-FL suppressed F. nucleatum-induced inflammatory cytokine overexpression in both HGECs and RAW 264.7 macrophages, and upregulated barrier-related proteins (ZO-1, Occludin) and MUC-1 gene expression in HGECs. In vivo studies demonstrated the inhibitory effect of 2′-FL on F. nucleatum-induced periodontal injury in Balb/c mice. Furthermore, 16S rRNA sequencing analysis demonstrated that 2′-FL modulated oral microbiota composition of healthy volunteers and significantly reduced the abundance of Fusobacterium. Full article

Excessive adipose tissue expansion contributes to metabolic dysfunction, highlighting the need to identify compounds that restrain adipocyte differentiation without causing nonspecific cytotoxicity. This study investigated whether 2-O-methylhonokiol suppresses adipogenesis in 3T3-L1 preadipocytes and examined its effects on adipogenic transcription, metabolic signaling, ER stress-related responses, kinase activity, and early cell cycle progression. 3T3-L1 cells were induced to differentiate with an MDI cocktail and treated with 25 or 50 µM 2-O-methylhonokiol during differentiation. Lipid accumulation was evaluated by Oil Red O staining, protein expression and phosphorylation were analyzed by immunoblotting, cell cycle distribution was assessed 24 h after MDI induction, and basal viability was measured using the CCK-8 assay. 2-O-methylhonokiol markedly reduced neutral lipid accumulation and suppressed key adipogenic regulators and maturation markers, including C/EBPβ, PPARγ, C/EBPα, FABP4, and FASN. At the signaling level, 2-O-methylhonokiol increased AMPKα phosphorylation without altering total AMPKα and reduced FASN expression, whereas mTOR phosphorylation was reduced at 50 µM. These findings suggest that 2-O-methylhonokiol is associated with metabolic and lipogenic signaling remodeling during adipocyte differentiation. 2-O-methylhonokiol also modified kinase-associated responses, increasing AKT and JNK phosphorylation while reducing the detectable phosphorylated ERK signal, with total AKT, ERK, and JNK remaining largely unchanged. ER stress-related signaling displayed a selective profile, characterized by increased IRE1α expression, XBP1s induction, elevated p-eIF2α, unchanged total eIF2α, and no compensatory increase in GRP78. During early adipogenesis, 2-O-methylhonokiol attenuated MDI-induced cell cycle redistribution by preserving a larger G0/G1 population and limiting progression toward later cell cycle phases, consistent with impaired mitotic clonal expansion. These effects occurred at concentrations that did not significantly reduce basal cell viability. Overall, 2-O-methylhonokiol suppresses 3T3-L1 adipogenesis by reducing adipogenic and lipogenic execution, accompanied by AMPK-associated metabolic remodeling, kinase signaling changes, selective ER stress-related responses, and restriction of early cell cycle progression. Further pathway-specific studies are required to define the causal contribution of each signaling axis. Full article

Background/Aim: Fibroblast growth factor receptor 4 (FGFR4) is a tyrosine kinase involved in cell growth, proliferation, and angiogenesis. While FGFR1–3 are well studied in cancer, FGFR4 remains relatively understudied, and the distribution of its mutations across cancers and patient populations is not well defined. Materials and Methods: A retrospective pan-cancer analysis was performed using the AACR Project GENIE v12 database via cBioPortal. Tumors with somatic FGFR4 mutations were included, excluding copy number alterations and structural variants. Mutations were grouped by hotspot (amino acid 401) and major protein domains. Comparative analyses assessed cancer type distribution, demographics, mutation burden, and co-occurring genomic alterations using chi-square testing with multiple comparison correction. Results: A total of 4565 tumor samples (4283 patients) were analyzed. FGFR4 alterations were observed across diverse malignancies, most commonly non-small cell lung cancer, colorectal cancer, and melanoma. Mutations clustered primarily in the tyrosine kinase and immunoglobulin I-set domains, with no significant variation in distribution across cancer types. Sex was not associated with the mutation group, while race and ethnicity showed significant differences. The FGFR4 hotspot 401 group demonstrated a higher mutation burden, driven by a subset of hypermutated tumors, and showed enrichment for co-occurring alterations in chromatin remodeling, DNA repair, tumor suppressor, and receptor tyrosine kinase genes; however, sensitivity analyses indicated this association was largely attributable to mutation burden rather than a mutation-specific effect. Domain-based mutation groups had lower mutation burdens and fewer co-alterations. Conclusions: FGFR4 alterations occur across a broad range of cancers with consistent domain-level patterns. The hotspot 401 mutation shows a higher mutation burden and co-alteration frequency driven largely by a subset of hypermutated tumors, rather than acting as an isolated driver. Full article

Fusarium head blight (FHB) caused by Fusarium graminearum leads to huge yield losses and mycotoxin contamination in wheat globally. Paenibacillus polymyxa with strong antagonistic activity was preliminarily identified. To clarify the key antifungal component, an extracellular protein was purified via ammonium sulfate precipitation, DEAE-52 anion-exchange and Sephadex G-75 gel filtration chromatography. SDS-PAGE showed a single band at 76 kDa. liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis confirmed this protein belongs to glycosyl hydrolase family with 86% sequence coverage. Biochemical characterization showed that the crude protein was stable at 40–90 °C and pH 3.0–9.0, sensitive to proteinase K, trypsin and neutral protease. The purified 76 kDa protein exhibited antifungal activity against F. graminearum. The gene encoding this protein was cloned and expressed in Escherichia coli. The renatured recombinant protein p76kd showed comparable antifungal activity to the native protein. This study purified and characterized a 76 kDa protein annotated as a glycosyl hydrolase via LC-MS/MS peptide matching; its antifungal function is presumed to originate from the conserved glycosyl hydrolase domain according to existing homologous research, which is distinct from previously reported lipopeptides or uncharacterized complexes. This protein provides a promising candidate for the biocontrol of FHB and related fungal diseases in cereal crops. Full article

N-acetylornithine aminotransferase (AcOAT) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that catalyzes a key transamination step in arginine biosynthesis. In cyanobacteria, arginine metabolism is closely associated with nitrogen assimilation and storage, yet biochemical information on cyanobacterial AcOATs remains limited. In this study, the AcOAT encoded by the cce_3094 gene from Crocosphaera subtropica ATCC 51142 (CsAcOAT) was cloned, heterologously expressed, purified, and systematically characterized. Recombinant CsAcOAT was obtained as a soluble protein with an apparent molecular mass of approximately 43 kDa. Steady-state kinetic analysis showed that CsAcOAT catalyzed transamination between N-acetylornithine (AcOrn) and α-ketoglutarate (α-KG), with apparent K_M values of 0.17 ± 0.03 mM for AcOrn and 0.020 ± 0.003 mM for α-KG, indicating a higher affinity for α-KG. The enzyme exhibited optimal activity at pH 8.5 and 30 °C, retained relatively high activity over a broad temperature range of 0–50 °C, and was activated by Zn²⁺ and Co²⁺ but inhibited by Ni²⁺. Structural analysis based on homology modeling, molecular docking, and molecular dynamics simulations suggested a conserved PLP-dependent aminotransferase fold and a stable binding mode for the PLP-AcOrn complex in the active-site pocket. Site-directed mutagenesis further demonstrated that Gly114, Asp239, Lys268, and Thr296 are indispensable for catalytic activity, whereas Ser113, Ala115, and Gln242 make important contributions to catalytic turnover and cofactor-assisted catalysis. These results provide biochemical and structural characterization of CsAcOAT, expand current knowledge of cyanobacterial AcOATs, and offer a useful basis for future studies on arginine metabolism and nitrogen storage in diazotrophic cyanobacteria. Full article

Background/Objectives: This study aimed to evaluate and compare the clinical characteristics and outcomes of patients with methicillin-susceptible Staphylococcus aureus (MSSA) and streptococcal native joint septic arthritis (NJSA). Methods: This retrospective multicenter study included adult patients with NJSA from three tertiary care hospitals between 2004 and 2023. Patients were categorized into three groups based on bacterial virulence and differences among streptococcal species: MSSA, non-viridans streptococci, and viridans streptococci. Results: A total of 213 NJSA cases were identified, comprising 164 MSSA, 35 non-viridans streptococcal, and 14 viridans streptococcal cases. Non-viridans streptococcal NJSA exhibited significantly more acute clinical features associated with systemic inflammation, including frequent fever, leukocytosis, thrombocytopenia, elevated C-reactive protein levels, higher total bilirubin levels, and acute kidney injury, compared to MSSA and viridans streptococcal NJSA. The clinical presentations were similar between the MSSA and viridans streptococcal groups. The non-viridans streptococcal group showed a higher incidence of concomitant bacteremia, but a lower proportion of positive joint culture results. Treatment approaches were consistent across the groups, except for a shorter duration of antibiotic therapy in the viridans group. Treatment failure rates were comparable: 9.8% for MSSA, 14.3% for non-viridans streptococci, and 21.4% for viridans streptococci. Conclusions: This study highlights the heterogeneous nature of streptococcal NJSA, with non-viridans streptococci presenting more aggressive clinical manifestations despite similar treatment responses across groups. These findings challenge conventional views on streptococci as a less virulent pathogen than MSSA and emphasize the need for diagnostic and management strategies tailored to the unique pathogenic traits of these bacteria. Full article

Staphylococcus pseudintermedius is a common opportunistic pathogen in companion animals and a leading cause of skin and soft tissue infections (SSTIs). Despite its clinical relevance, the genomic determinants underlying pathogenicity and the transition from commensal carriage to invasive infection remain poorly understood. This study aimed to identify the genomic determinants of SSTI pathogenic potential in S. pseudintermedius and to determine whether pathogenicity is driven by single, major-effect virulence genes or by polygenic genome-wide genetic architecture. Using accessory gene-based and unitig-based genome-wide association studies (GWASs), employing a linear mixed model, across a genetically diverse collection of S. pseudintermedius isolates spanning multiple phylogenetic clades, we found that disease and carriage isolates showed no phylogenetic clustering. SSTI pathogenicity exhibited high narrow-sense heritability. Surface-associated LPXTG-anchored proteins, particularly spsF, harbored the strongest associations, with additional signals in iron metabolism (narH, sufB) and oxidative stress tolerance (ahpC). Random Forest classification validated GWAS signals. SSTI pathogenicity in S. pseudintermedius reflects a polygenic architecture driven by cumulative variation across surface-associated, metabolic, and stress-response loci, shifting focus from single virulence genes to genome-wide genetic variation. Full article

Background/Objectives: Sensory nerves, as essential peripheral nerves, innervate bone and release various neuroactive substances—including neurotransmitters, neuropeptides, and neurocrine factors—that participate in bone growth, remodeling, and metabolism. Interleukin-1 receptor antagonist (IL1RN), an endogenous anti-inflammatory mediator, is a key regulatory molecule in the pathogenesis of inflammatory diseases such as osteoarthritis and rheumatoid arthritis. However, its role as a sensory neurocrine factor in the regulation of bone tissue has rarely been investigated. This study aimed to explore the regulatory effects of sensory nerve–derived IL1RN on bone tissue. Methods: A dorsal root ganglion (DRG)-targeted delivery system was developed using DNA origami technology to load IL1RN protein or IL1RN-targeting siRNA and was functionalized with a DRG-homing peptide. Bone defect and age-related bone loss models were established in C57BL/6 mice to preliminarily investigate the regulatory role of IL1RN secreted from sensory nerve endings in bone tissue. Results: IL1RN suppressed bone resorption and promoted new bone formation at defect sites. In the age-related bone loss model, IL1RN preserved the integrity of the growth plate. These findings indicate that sensory nerve–derived IL1RN may participate in the regulation of bone repair and skeletal homeostasis. Conclusions: IL1RN may serve as a potential therapeutic target for DRG-mediated regulation of bone repair. These findings suggest that DRG-targeted modulation of IL1RN may represent a potential approach for investigating and regulating sensory nerve–associated bone repair. Full article

Graphene oxide (GO)-based nanomaterials functionalized with targeting ligands are promising platforms for selective cancer drug delivery. Among relevant targets, integrin α_Vβ₃ is a highly overexpressed receptor in several solid tumors and is commonly targeted using cyclic Arg-Gly-Asp (cRGD) peptides. However, the molecular details governing the interaction between cRGD-functionalized GO dots and integrins remain poorly understood. In this work, all-atom molecular dynamics simulations are employed to investigate the interaction between integrin α_Vβ₃ and a nanocarrier composed of a GO dot coated with polyethylene glycol (PEG) and functionalized with cRGD ligands. Multiple 1 μs simulation replicas are used to characterize both specific ligand recognition and non-specific nanocarrier/receptor interactions. The simulations show that cRGD binding within the integrin-binding pocket is stable, indicating that the nanocarrier does not impair receptor recognition. Beyond cRGD-mediated binding, both PEG-cRGD chains and GO itself establish additional contacts with the protein, whose nature and distribution are modulated by the relative orientation of the GO plane. Overall, the structural dynamics of integrin α_Vβ₃ remains preserved upon nanocarrier binding. These findings provide atomistic insights into the interplay between ligand-mediated and multivalent surface-mediated interactions of GO-based nanocarriers with integrins for the rational design of selective nanocarriers for cancer therapy. Full article

The demand for sustainable nutrients and bioactive compounds has increased interest in underutilized wild plants. Forestiera tomentosa, a Mexican drupe-bearing species, is largely unexplored. This study evaluated the proximate composition, physicochemical and functional properties, phenolic profile, antioxidant capacity, and toxicological safety of F. tomentosa fruit. The fruit showed high carbohydrate content [71.94% dry weight (DW)], with notable crude fiber (7.90% DW), protein (7.39% DW), and lipid (4.30% DW) contents. Analysis revealed a mildly acidic pH (5.66), titratable acidity of 0.32%, and total soluble solids of 2.33 °Brix. The fruit powder had a low water activity (0.42) and a favorable water solubility index (56.10%), oil absorption (4.54%), and foaming capacity (19.71%). The fruit contained high levels of soluble phenols (280.42 mg GAE/g DW), flavonoids (98.89 mg CE/g DW), anthocyanins (54.53 mg C3G/g DW), and condensed tannins (94.05 mg CE/g DW). High-performance liquid chromatography identified 20 phenolic compounds, with 3-(4-hydroxyphenyl) propionic acid, syringic acid, catechin, epicatechin, and gallocatechin being predominant. The fruit showed significant radical scavenging and reducing potential (DPPH, ABTS, and FRAP). Toxicological evaluation using the Artemia salina bioassay showed a 100% survival rate across all concentrations, indicating no acute toxicity. In silico ADMET predictions revealed favorable pharmacokinetic properties, including high intestinal absorption and compliance with Lipinski’s rule of five. These findings position F. tomentosa as a promising, non-toxic source of functional ingredients for the food, nutraceutical, and pharmaceutical industries, supporting biodiversity conservation and sustainable resource utilization. Further studies are needed to evaluate the potential health benefits of this fruit in vitro and in vivo. Full article

Background and objective: A huge part of cosmetics research is devoted to the identification of new molecules and new ingredients which could prevent skin aging. Crithmum maritimum has attracted interest in the cosmetic field because it has been used since antiquity in traditional medicine and is traditionally consumed in Mediterranean regions. However, data about demonstrated efficacy on living cells remain sparse. To better understand the potential of this plant for the cosmetics industry, we aimed to investigate in vitro some key properties in line with anti-aging skin care. Methods and results: Molecular results demonstrated an impressive antioxidant effect which was confirmed in vitro on living keratinocytes with a decrease of 50% of oxidative stress measured with the fluorescent CM-H₂DCFDA probe. Additionally, an inhibitory effect around 20% was observed on isolated collagenase and elastase, highlighting the ability of C. maritimum to preserve the skin matrix. Lastly, anti-inflammatory properties were explored at protein levels by ELISA method, indicating a clear decrease of six inflammatory mediators, IL-6, IL-8, IL-18, CXCL9, CXCL10, and CCL5, on stressed keratinocytes. These observed decreases span from 20% up to 75% in the case of the IL-18. Conclusions: All together, these results reveal how efficient C. maritimum extract could be to alleviate signs of aging. Full article

Maternal exposure to nanoplastics is a growing concern, but its effects on offspring cardiac development and the relative importance of prenatal and lactational exposure remain unclear. Pregnant C57BL/6J mice were orally exposed to 50 nm polystyrene nanoplastics at 3, 15, or 75 μg/g body weight from gestational day 1 to postnatal day 21. A cross-fostering design was used to distinguish gestational exposure from lactational exposure. Maternal polystyrene nanoplastic exposure caused dose-dependent cardiac dysfunction in offspring, including reduced ejection fraction and fractional shortening, increased myocardial injury markers, cardiomyocyte hypertrophy, and fibrosis. Cross-fostering showed that lactationally exposed offspring exhibited more severe cardiac abnormalities than offspring exposed only during gestation, indicating that the nursing period may represent a more vulnerable window. In male offspring, polystyrene nanoplastic exposure was also associated with gut microbiota dysbiosis and cardiac transcriptomic changes. Enrichment analysis identified downregulation of genes related to AMP-activated protein kinase signalling, and integrated microbiome–transcriptome analysis suggested associations between altered gut taxa and cardiac differentially expressed genes. These findings indicate that maternal polystyrene nanoplastic exposure induces offspring cardiac developmental toxicity, with stronger effects during lactation, and suggest the involvement of gut microbial and cardiac molecular remodelling. Full article

Molecule Interacting with CasL 1 (MICAL1) is a flavoprotein monooxygenase that promotes filamentous actin (F-actin) depolymerization. Transcriptomic studies have linked MICAL1 downregulation to skeletal muscle atrophy and muscular dystrophy, yet its functional contribution to myogenesis remains unexplored. We found that MICAL1 protein increased progressively during myogenic differentiation of C2C12 cells, reaching a maximum on day 5 in parallel with myosin heavy chain (MyHC). siRNA-mediated MICAL1 silencing produced an ~1.7-fold accumulation of F-actin, while total β-actin protein remained unchanged, indicating a shift in the G-/F-actin equilibrium toward polymerization rather than altered actin expression. The accumulated F-actin reduced YAP1 phosphorylation, promoted its nuclear translocation, and increased the expression of the YAP1 target gene CTGF. MICAL1 depletion also enhanced myoblast proliferation: EdU incorporation and cell viability increased, and PCNA, CCNB1, and CCND1 protein expression was upregulated, while the cell cycle distribution shifted toward the G2/M phase, with a reciprocal loss in G0/G1. Concurrently, MICAL1 knockdown suppressed MyoD, Myogenin, and MyHC throughout differentiation and severely impaired myotube formation, with reductions in the fusion index, myotube area, and length. We conclude that MICAL1 is required for the proliferation-to-differentiation switch in myoblasts and that its activity restrains F-actin-driven YAP1 signaling to permit timely myogenic commitment. MICAL1 may therefore represent a candidate for further investigation in muscle-wasting diseases. Full article

Dysgeusia is a clinically consequential, but still under-standardized, toxicity of cancer treatment. In the immunotherapy era, taste disturbances are increasingly relevant for patients receiving immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapies and T-cell-redirecting bispecific antibodies, with G protein-coupled receptor family C group 5 member D (GPRC5D)-directed treatment in multiple myeloma representing a particularly instructive high-burden model. We performed a structured critical narrative review with evidence mapping. PubMed/MEDLINE was searched from database inception to June 2026, complemented by citation tracking in Google Scholar, ClinicalTrials.gov searches and guideline documents relevant to oncology nutrition, oral supportive care and cancer-related taste dysfunction. Search concepts covered cancer-related dysgeusia, immunotherapy-associated oral toxicity, GPRC5D/talquetamab-associated dysgeusia, oncology nutrition, oral–gut microbiome biology, natural taste modulators and miraculin-based interventions. Dysgeusia can reduce appetite, food enjoyment, dietary diversity and protein energy intake, thereby contributing to weight loss, malnutrition risk, distress, social withdrawal and, in severe cases, treatment modification or discontinuation. Available evidence is heterogeneous: general cancer-treatment-associated dysgeusia is supported by broader observational and interventional literature; immunotherapy-associated dysgeusia is less systematically characterized; and GPRC5D/talquetamab-associated dysgeusia represents the most clinically visible and target-specific immunotherapy-associated phenotype. Emerging pilot data suggest that dried miracle berry or miraculin-containing products may improve selected taste perception and nutritional parameters in cancer-related dysgeusia, but direct evidence in immunotherapy-associated dysgeusia is not yet established. We, therefore, propose a claim-disciplined precision supportive-care framework integrating systematic taste phenotyping, early nutritional risk assessment, oral health evaluation, microbiome-aware but hypothesis-generating endpoints, individualized flavor and texture adaptation, cautious use of natural taste modulators in selected patients and iterative monitoring of patient-centered outcomes. Future trials should test whether dysgeusia-focused nutritional and taste-modulating supportive care interventions can improve intake, quality of life and treatment persistence without compromising immunotherapy safety or efficacy. Full article

Orf virus (ORFV) is a major pathogen in goats and sheep, and control currently depends mainly on commercial live vaccines. Although mRNA vaccines have revolutionized human medicine, their use in veterinary settings is largely unexplored. In this study, an mRNA vaccine candidate encoding the ORFV F1L protein (F1L-mRNA-LNP) was developed via in vitro transcription and encapsulated in lipid nanoparticles. BALB/c mice were divided into five groups (n = 14 each): three receiving different doses of F1L-mRNA-LNP (5, 10, or 15 μg), one receiving a commercial live vaccine (CV), and a PBS control group. Mice were immunized intramuscularly and boosted after 14 days; immune responses were assessed 14 days later following ARRIVE 2.0 guidelines. Both the F1L-mRNA-LNP and CV vaccines induced specific antibodies versus PBS (p < 0.01). The 10 μg mRNA group showed Th1 cytokine and CD8⁺ T cell responses comparable to CV (p > 0.05), whereas IL-4 (Th2) was significantly higher in the CV group (p < 0.05). Neutralizing antibody titers did not differ between groups, indicating that the mRNA vaccine induces comparable Th1 cellular immunity but weaker Th2 humoral immunity. Upon ORFV challenge, the 10 μg F1L-mRNA-LNP vaccine protected BALB/c mice, as evidenced by stable body weight, no clinical symptoms, and reduced viral load, with efficacy comparable to CV (p > 0.05). This study provides strong evidence supporting the optimization of ORFV mRNA vaccines and highlights the translational potential of the F1L-mRNA-LNP candidate vaccine for veterinary applications. Full article