Search Results (6,985)

Pseudorabies (PR) is an acute and highly contagious disease caused by the pseudorabies virus (PRV). This virus has a wide range of susceptible hosts and has caused major economic losses to the global swine industry. While rosmarinic acid possesses broad antioxidant and antiviral properties, its efficacy against PRV has remained unexplored. Therefore, this study aimed to evaluate the anti-PRV activity of rosmarinic acid and to elucidate its underlying mechanism, with a focus on the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. The results revealed that rosmarinic acid exhibited potent, concentration-dependent antiviral activity in vitro, with a half-maximal inhibitory concentration (IC50) of 0.02654 mg/mL, a half-maximal cytotoxic concentration (CC50) of 0.1043 mg/mL, and a selectivity index (SI) of 3.9. Rosmarinic acid inhibited virus adsorption, entry, and intracellular replication. It also significantly suppressed the expression of the gB protein. In a mouse model, rosmarinic acid treatment (200 mg/kg) significantly enhanced the survival rate to 28.5%. This treatment reduced the viral load in the brain, lungs, kidneys, heart, and spleen. It also alleviated the tissue damage caused by PRV infection. Furthermore, rosmarinic acid counteracted PRV-induced oxidative stress by elevating the activity of the antioxidant factors SOD and CAT and reducing the level of the oxidative factor MDA. Combined network pharmacology and molecular docking analyses predicted the Nrf2 signaling pathway as a key target for rosmarinic acid. Subsequent mechanistic studies confirmed that rosmarinic acid upregulated the expression of the Nrf2, HO-1, GPX, SOD, and CAT genes, as well as Nrf2 and HO-1 proteins, thereby promoting the nuclear translocation of Nrf2. These results identify rosmarinic acid as a promising anti-PRV agent that acts through multi-phase viral inhibition and activation of the Nrf2-mediated antioxidant defense, suggesting its potential as a novel pharmacological strategy against PRV. Full article

Cancer remains one of the most significant global health challenges, with conventional treatments limited by side effects and resistance to drugs. The unique properties of metal–organic frameworks (MOFs), which offer high surface areas, tunable structures, and biodegradable properties, make them promising candidates for cancer therapy. This review focuses on MOF-based drug delivery systems for cancer treatment in biomedical applications. This article discusses various synthesis methods, drug-loading strategies, and cytotoxicity considerations. The relationship between the basic chemistry of MOFs and their biomedical applications is elucidated by how each feature directly affects MOF performance in cancer drug delivery. Therefore, this review is a practical and complete guide for researchers working to translate MOFs into effective cancer treatments. Moreover, the role of stimuli-responsive MOFs in cancer therapy is highlighted, along with recent studies demonstrating the effectiveness of MOF-based drug delivery systems. Overall, MOFs offer opportunities for advancing cancer treatment and controlled drug delivery. Full article

Background: Synthetic vascular scaffolds often exhibit limited mechanical performance and low hydrophilicity, which compromise early vascular integration and increase susceptibility to bacterial colonization. This study developed 3D-printed scaffolds based on poly(L-co-D,L-lactide)–poly(trimethylene carbonate) (PLDLA–TMC) with polyethylene glycol 400 (PEG) to modulate mechanical and interfacial properties and coated with poly(hexamethylene biguanide) (PHMB) to confer antibacterial activity. Methods: PLDLA–TMC scaffolds modified with PEG 400 and coated with PHMB were prepared and systematically characterized to assess their structural, thermal, mechanical, and antimicrobial properties. PHMB coatings (3%, 6%, and 12% w/w in hydroxypropyl methylcellulose, HPMC) were applied and evaluated for drug release, cytotoxicity, and activity against Staphylococcus aureus. Biocompatibility was tested in an endothelial cell and myoblast co-culture. Results: Incorporation of 2% PEG increased the tensile strength from 0.14 ± 0.10 MPa for scaffolds containing 0.5% PEG to 0.79 ± 0.12 MPa and promotes a more elastic scaffold behavior. PHMB at 12% caused cytotoxicity (7.70 ± 0.37% cell viability). The 3% PHMB coating produced a 12.5 ± 0.1 mm inhibition zone but exhibited burst release within 1 h, whereas the 6% coating maintained cell viability (72.95 ± 1.10%), produced a 13.1 ± 0.2 mm inhibition zone, and provided sustained antimicrobial release over 7 days. Scaffolds supported organized adhesion and proliferation of endothelial cells and myoblasts. Conclusions: 3D-printed PLDLA–TMC scaffolds containing 2% PEG and coated with 6% PHMB combined improved mechanical performance, sustained antimicrobial release, antibacterial activity, and biocompatibility in an in vitro vascular model. Full article

Algal carotenoids play a promising role in handling chronic diseases due to their diverse bioactive properties, including anti-inflammatory, antioxidant, and anticancer effects. This study assesses the activity of the antioxidant xanthophyll diatoxanthin (Dt), derived from marine diatoms, against triple-negative breast cancer (TNBC) cells using in vitro models, gene expression evaluation, and explores its role in potentiating the cytotoxic effect of chemotherapy. Dt exhibited selective activity against MDA-MB-231 and BT-549 TNBC cells at concentrations ≥12.5 ng/mL, with maximal effects observed at 25 ng/mL while sparing human umbilical vein endothelial cells (HUVECs) at these doses. When combined with doxorubicin (0.1–0.5 μM), Dt enhanced the anti-tumor efficacy in both TNBC cell lines, further reducing cell viability compared with doxorubicin alone (p < 0.05–0.001). Dt also exerted its activity in inhibiting migration and chemotaxis by approximately 30–50% compared with the controls (p < 0.01) and suppressing 3D-tumor spheroid growth at day 12 (up to >50% reduction, p < 0.001). Notably, secretome analysis revealed Dt-induced changes in inflammatory, oxidative and angiogenic mediators, highlighting its ability to modulate the TNBC microenvironment. Dt also downregulated key pro-survival, pro-angiogenic and pro-tumorigenic genes in both TNBC cell lines, supporting its role in disrupting oncogenic pathways. Angiogenesis-related genes were significantly reduced. Dt also decreased the expression of angiogenic mediators in HUVECs, supporting Dt’s role in inhibiting tumor vascularization. Results on gene expression regulation were also confirmed by RNA-Seq analysis. These findings pose Dt as a promising chemopreventing candidate in the challenging fight against TNBC, a well-known type of cancer that is aggressive and resistant to conventional therapies, targeting critical pathways for tumor survival, such as inflammation, angiogenesis, tumor cell growth, and cell migration. Given its selective activity against TNBC cells, ability to enhance chemotherapy efficacy, and modulation of the tumor microenvironment, Dt holds promise as a complementary drug for cancer prevention and interception. Future studies should focus on validating these effects in vivo and exploring Dt’s potential in combinatorial treatment strategies for cancer. Full article

Malignant gliomas, including glioblastoma multiforme (GBM) and grade 4 astrocytoma, are the most common types of brain tumors in adults. Standard treatment for gliomas includes adjuvant chemotherapy, typically based on temozolomide, combined with radiotherapy. However, its effectiveness is severely hindered by the limited ability of drugs to cross the blood–brain barrier and by the hyperactivation of the canonical Wnt signaling pathway, which drives tumor cell survival. Therefore, innovative drug combinations and novel delivery strategies are crucial for overcoming these barriers. Polymeric micelles represent a promising approach for enhancing drug delivery to brain tumors. This study aimed to obtain micelles containing cannabidiol (CBD), celecoxib (CELE), and temozolomide (TMZ), as well as their combinations, and to verify their anti-glioma properties. The study involved optimizing the micelle composition, incorporating active ingredients, and assessing the temporal stability of the resulting nanocarriers under varying temperature conditions. The GBM cell line U-138 MG and astrocytoma cell line U-87 MG were used to evaluate the biologic effects of the tested micelles. Cytotoxicity was assessed using the MTT assay, and flow cytometry was used to analyze the effect of the micelles on apoptosis. Western blot analysis was employed to assess the impact of the tested nanoformulations on the Wnt/β-catenin signaling pathway. The optimized micelles demonstrated strong cytotoxic and proapoptotic effects, accompanied by attenuation of the Wnt/β-catenin pathway. These preliminary findings support the therapeutic potential of polymeric micelles for treating malignant gliomas; however, further in vitro and in vivo studies are required to confirm their clinical applicability. Full article

Background: Gum Arabic (GA) is a natural polysaccharide widely recognized for its antioxidant and anti-inflammatory properties; however, its functional behavior as a biopolymeric gel and the mechanisms underlying its selective effects on cancer-related redox microenvironments remain insufficiently characterized. It is imperative to note that the interaction between its physicochemical properties and its biological activity in colorectal cancer remains to be fully clarified. Methods: This study aimed to evaluate the antineoplastic potential of GA in human colorectal cancer (CRC) cell lines (HT-29 and HCT-116) compared to normal fibroblasts (MRC-5) using the MTS assay. Oxidative stress-related molecular responses were assessed by quantitative PCR analysis of GPX4, GSTA2, CAT, NFKB, and SOD1 expression. In parallel, extracellular concentrations of key metal ions (Fe²⁺, Zn²⁺, Mn²⁺, Mg²⁺, Cu²⁺, and Al³⁺) were quantified following GA exposure. To establish its functional gel characteristics, rheological measurements were performed to assess viscosity and shear-dependent behavior, and USP-compliant in vitro kinetic studies were conducted to evaluate time-dependent release properties. Results: GA induced dose-dependent cytotoxicity in HT-29 and HCT-116 colorectal cancer cells, while MRC-5 fibroblasts exhibited comparatively higher viability across the tested concentration range, indicating reduced sensitivity in normal cells. Rheological analysis revealed concentration- and ion-dependent viscoelastic behavior, identifying a 10% (w/w) GA formulation as optimal due to its balanced low-shear viscosity and controlled shear-thinning properties. Kinetic studies demonstrated a defined, diffusion-governed release profile under physiologically relevant conditions. At the molecular level, significant upregulation of GPX4 and GSTA2 was observed in both cancer cell lines, whereas NFKB expression increased selectively in HT-29 cells, with no notable changes in CAT or SOD1 expression. Additionally, GA treatment resulted in marked increases in Fe²⁺, Zn²⁺, and Mn²⁺ levels, indicating modulation of the redox–ionic microenvironment. Conclusions: These findings demonstrate that GA functions as a natural, ion-responsive biopolymeric system with defined rheological and kinetic properties, capable of selectively targeting colorectal cancer cells through coordinated genetic and ionic regulation of oxidative stress. Collectively, the results position GA as a promising functional gel-based platform for future redox-modulated therapeutic strategies in colorectal cancer. Full article

Glycyrrhiza glabra L. (Fabaceae) is a plant species with already demonstrated countless biological properties and many more still to be discovered. Here, root sample extracts from different geographical areas were compared based on their phytochemical profiles and biological activities. Both raw and hydrolysate extracts, as well as 18β-glycyrrhetinic acid, glycyrrhizin, and isoliquiritigenin, considered as the main licorice secondary metabolites, were screened for antiproliferative and anti-migration properties in MCF-7, MDA-MB-231, A2780, HeLa, SiHa, and C33A breast and gynecological cancer cell lines. Hydrolysate extracts showed higher cytotoxicity than the raw extracts at the same final concentrations, 30 and 60 µg/mL, respectively. Among the standards, isoliquiritigenin showed the most pronounced cytotoxic activity, with inhibitory percentages exceeding 70% in each of the investigated cell lines at the lowest tested dose of 30 µg/mL. Then, the most effective extracts in the MTT assay, LIT2-H and LMO-H, were screened in a wound-healing test, demonstrating efficacy against ovarian (A2780) and cervical (C33A) cancer cell lines after 24 and 48 h of exposure. Full article

The development of effective inhalable drugs remains a key challenge in the treatment of pulmonary diseases, due to the physiological barriers of the respiratory tract and the lack of predictive models that accurately reproduce the human lung environment. In this context, liposomes (LP) have emerged as promising nanocarriers for pulmonary drug delivery due to their high biocompatibility, surfactant-like composition, capacity to encapsulate both hydrophilic and lipophilic drugs, and potential to provide sustained drug release while reducing systemic toxicity. This study evaluates the influence of size and PEGylation on their physicochemical properties, cytotoxicity, interaction with the pulmonary mucus, and cellular internalisation. LP of 100 nm (LP 100), 200 nm (LP 200), and 600 nm (LP 600) were characterised physiochemically and evaluated in pulmonary cell lines (A549 and Calu-3) exposed in liquid–liquid interface (LLI) and air–liquid interface (ALI) by nebulisation. In addition, artificial pulmonary mucus (APM) was employed to analyse LP penetration through the pulmonary mucus barrier. Results indicate that LP 100 exhibits greater colloidal stability, lower cytotoxicity, and sustained migration through the APM over time with respect to larger particles. PEGylation of LP 100 (LP-PEG) further increases their stability and ability to penetrate the APM, although cellular internalisation is reduced due to the steric effect of the PEG coating. These findings highlight the importance of adjusting the size and surface modifications of LPs according to the therapeutic target of the drug, optimising their persistence on the epithelial surface or their cellular uptake. Full article

Annurca apple extract is gaining growing attention for its beneficial properties, particularly its outstanding antioxidant activity. Using a combination of biophysical, cell, and molecular biology techniques, this study investigates the sustainable valorization of Annurca apple by-products at different ripening stages and their role in the formation of advanced glycation end-products (AGEs), as well as in protection against AGE-related cytotoxicity. AGEs are a class of compounds formed by non-enzymatic reactions between reducing sugars and proteins, lipids, or nucleic acids. They can be produced endogenously or ingested through dietary sources and tobacco smoke. AGEs accumulate in nearly all mammalian tissues and are linked to various health issues, such as diabetes and its related complications, cardiovascular disease, and neurodegenerative disorders. Our data show that Annurca apple by-products at different ripening stages differentially counteract AGEs’ formation by inhibiting protein glycation and protect against AGE-induced cytotoxicity in endothelial cells. In particular, the extracts reduce AGE-induced reactive oxygen species (ROS) production, thereby inhibiting MAPK signaling pathways and caspase-3 activation. Moreover, ripening significantly enhances the concentration of bioactive compounds and the extent of cellular protection. This study highlights new beneficial properties of Annurca apple extracts and suggests that adopting nutritional interventions may support health and potentially reduce the risk of complications associated with AGE accumulation. Full article

Background/Objectives: Antimicrobial resistance (AMR) presents a medical risk as well as a significant global socioeconomic challenge. Key contributors to AMR include the excessive use and incorrect application of antibiotics in humans and agriculture, nosocomial infections, and the absence of new classes of antibiotics. Methods: Novel dibrominated tricyclic flavonoids have been synthesized from the corresponding 3-dithiocarbamic flavanones and their antimicrobial and cytotoxicity properties have been investigated. Results: It has been found that these tricyclic flavonoids exhibit strong antimicrobial properties against clinically relevant pathogens such as Staphylococcus aureus, Acinetobacter baumannii, and Escherichia coli with MIC and MBC values against S. aureus ATCC 25923 as low as 0.12 µg/mL and 1.9 µg/mL, respectively. Conclusions: The synthetic tricyclic flavonoids exhibit strong antibacterial activity against selected WHO priority pathogens, including Staphylococcus aureus and Acinetobacter baumannii, surpassing the efficacy of both natural and synthetic flavonoids and several conventional antibiotics. Full article

The development of photocurable hydrogel biomaterial inks with suitable rheology, low cytotoxicity, and tuneable mechanical properties is essential for reliable biofabrication. This study aimed to formulate PEGDA–gelatine–collagen inks using lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as photoinitiator. Rheological characterisation and flow-model fitting were performed, mechanical stiffness modulation under different light intensities was evaluated, complex structures were printed using direct extrusion and FRESH methodologies, and PEGDA/LAP extractables were quantified by NMR after controlled washing procedures. In vitro assays assessed cell viability and proliferation on the resulting scaffolds. The Herschel–Bulkley model best described the flow behaviour across formulations; while viscoelastic measurements showed that increasing light intensity progressively enhanced hydrogel stiffness, enabling fine control over final mechanical properties. NMR analysis showed that washing removed a substantial fraction of residual LAP, in agreement with the biological findings: fibroblasts failed to survive on unwashed scaffolds but exhibited robust proliferation and recovered their characteristic elongated morphology on washed constructs. Among all inks, PeGeCol_10_2 provided the best combination of shear-thinning behaviour, structural integrity, low residual photoinitiator, and tuneable mechanics. Using this formulation, we successfully printed large anatomical models with high fidelity and excellent handling properties, underscoring its potential for soft-tissue prosthetics and broader tissue-engineering applications. Full article

Background: Malva sylvestris (the common mallow) is an herbaceous species widely used in ethnobotanical practices to treat gastrointestinal, hepatic and urinary inflammation. Objectives: Despite these beneficial effects on human health, the antineoplastic potential of this plant has not yet been fully explored. Thus, in the present study, two human colon cancer cell lines (i.e., HCT-116 and Caco-2) were treated with an extract obtained from M. sylvestris flowers (MFE), whose composition in terms of phytochemicals and microRNAs has been recently published by our research group, to explore its potential bioactivity. Methods/Results: MTT and Trypan blue assays demonstrated that MFE reduced tumour cell growth without causing significant cytotoxicity or apoptosis. Following the diphenylboric acid 2-aminoethyl ester-induced fluorescence of some plant metabolites, microscopy analysis proved that MFE components crossed the cell membranes, accumulating into nuclei. Wound assay and transwell tests documented that MFE was also able to reduce cell motility and invasiveness. In both cell lines qPCR experiments demonstrated that MFE caused the over-expression of factors, like VIMENTIN and E-CADHERIN, which negatively influence epithelial–mesenchymal transition in colon cancers. However, the effects of MFE appeared to be time-, dose- and cell type-dependent. In fact, the treatment induced senescence in P53-null Caco-2 cells (i.e., ROS, β-galactosidase and P21^WAF1/Cip1) and a premise of differentiation (i.e., P27^Kip1) in P53-wild-type HCT-116 cells, also via the CDK2/c-MYC/AKT axis, justifying its antiproliferative property. In parallel, the transfection of tumour cells with pure synthetic miR160b-5p—a microRNA identified in M. sylvestris flowers and predicted to target the human CDK2 transcript—resulted in gene silencing, thereby suggesting its central role in mediating the cross-kingdom effects of MFE on the investigated cancer models. Conclusions: Overall, these findings open new perspectives on the common mallow as a source of potential antimetastatic compounds and on the possible use of its plant microRNAs in the development of gene therapies. Full article

Although Simarouba glauca DC. has been recognized for its therapeutic properties, its anticancer effects against oral cancer have not been adequately investigated. The present study aimed to evaluate the activity of S. glauca leaf extracts against oral squamous cell carcinoma (OSCC). S. glauca leaves were extracted using solvents of increasing polarity, and the resulting fractions were evaluated for their phytochemical composition, antioxidant activity, and cytotoxic effects. Among all extracts, the S. glauca hexane extract (SGHE) exhibited the most potent anticancer activity against cell lines representing OSCC (CAL-27), cervical cancer (HeLa), and mouse mammary tumors (4T1). Bioactivity-guided fractionation identified D-erythro-Sphinganine as a major constituent present in hexane extract, possibly contributing to anticancer activity. But since the anticancer activity of crude hexane extract is superior compared to isolated D-erythro-Sphinganine, we predict a synergistic interaction among the multiple bioactive compounds present in the crude hexane extract. Hence, further studies were carried out with crude hexane extract. Mechanistic studies have shown that the anticancer activity of hexane extract is due to its ability to (a) alter cell cycle progression, (b) trigger apoptosis, and (c) inhibit cell migration in CAL-27 cells. Overall, these findings indicate that the hexane extract of S. glauca leaf possesses multi-target anticancer potential and warrants further mechanistic and in vivo investigations. Full article

Background: Boron neutron capture therapy (BNCT) represents a highly selective therapeutic modality for recalcitrant cancers, leveraging the nuclear reaction initiated by thermal neutron capture in boron-10 (¹⁰B) to deliver high-linear energy transfer radiation (α-particles and ⁷Li ions) directly within tumor cell boundaries. However, the widespread clinical adoption of BNCT is critically hampered by the pharmacological challenge of achieving sufficiently high, tumor-selective intracellular ¹⁰B concentrations (20–50 μg of ¹⁰B/g tissue). Conventional small-molecule boron carriers often exhibit dose-limiting non-specificity, rapid systemic clearance, and poor cellular uptake kinetics. Methods: To overcome these delivery barriers, we synthesized and characterized a novel dual-modality nanoplatform based on highly biocompatible, functionalized graphene oxide (GO). This platform was structurally optimized via covalent conjugation with high-boron content carborane clusters (dodecacarborane derivatives) for enhanced BNCT efficacy. Crucially, the nanocarrier was further decorated with plasmonic gold nanostructures (AuNPs), endowing the system with intrinsic surface-enhanced Raman scattering (SERS) properties, enabling real-time, high-resolution intracellular tracking and quantification. Results: We evaluated the synthesized GO@Carborane@Au nanoplatforms for their stability, cytotoxicity, and internalization characteristics. Cytotoxicity assays demonstrated excellent biocompatibility against the non-malignant human keratinocyte line (HaCaT) while showing selective toxicity (upon irradiation, if tested) and high cellular uptake efficiency in the aggressive human glioblastoma tumor cell line (T98G). The integrated plasmonic component allowed for the successful, non-destructive monitoring of nanoplatform delivery and accumulation within both HaCaT and T98G cells using SERS microscopy, confirming the potential for pharmacokinetic and biodistribution studies in vivo. Conclusions: This work details the successful synthesis and preliminary in vitro validation of a unique graphene oxide-based dual-modality nanoplatform designed to address the critical delivery and monitoring challenges of BNCT. By combining highly efficient carborane delivery with an integrated photonic trace marker, this system establishes a robust paradigm for next-generation theranostic agents, significantly advancing the potential for precision, image-guided BNCT for difficult-to-treat cancers like glioblastoma. Full article

Infectious diseases remain a major global health challenge, underscoring the need for safe and accessible antiviral therapies. Natural products, particularly marine macroalgae, are promising sources of bioactive compounds with antiviral properties. This study evaluated the antiviral activity of extracts from two red algae collected along the Portuguese coast: two life stages (tetrasporophyte and female gametophyte) of Chondracanthus teedei var. lusitanicus and the algae Osmundea pinnatifida. Antiviral effects were assessed against Coxsackievirus A12 (CVA12) and a lentivirus (LV) vector model. Extracts from both algae inhibited viral replication in vitro at non-cytotoxic concentrations. The tetrasporophyte extract of C. teedei exhibited virucidal activity against CVA12, and the results are consistent with interference with multiple stages of the viral life cycle, while also inducing an antiviral state in HEK-293T cells against LV infection. The female gametophyte extract affected early stages of CVA12 and LV infection and showed potential virucidal activity. O. pinnatifida demonstrated the strongest antiviral effects against both viruses. These findings highlight the antiviral potential of these red algal extracts and warrant further in vivo evaluation. Full article