Search Results (237)

The Nipah virus (NiV) is a zoonotic pathogen characterized by high fatality rates and pandemic potential, whereby there is an urgent need for developing safe and effective vaccines. However, the evaluation of NiV vaccine-induced immunity is hindered by the requirement of Biosafety Level-4 (BSL-4) containment. In this study, we developed a recombinant vesicular stomatitis virus (rVSV)-based pseudovirus-expressing NiV fusion (F) and attachment (G) glycoproteins using a luciferase reporter gene for bioluminescence detection. This pseudovirus was optimized for production in BHK-21 (WI-2) cells, and simultaneous incorporation of NiV-F and NiV-G onto the surface of the pseudotyped virus was confirmed via immunoprecipitation and Western blotting. We evaluated our pseudovirus-based neutralization assay using NiV-F-immunized mouse sera and a commercial anti-NiV-G antibody, confirming robust neutralization by the latter. To establish a BSL-2-compatible model for evaluating in vivo protective efficacy, we performed in vivo imaging, which revealed a marked reduction in the luminescence signal in NiV-G-immunized mice compared to naïve controls, indicating vaccine-induced protection. Our study established an integrated in vitro and in vivo pseudovirus platform using rVSV that enables safe, quantitative, and BSL-2-compatible evaluation of NiV vaccine candidates. This model offers a valuable tool for preclinical screening of vaccine-induced neutralizing antibody responses and protective efficacy. Full article

With the rapid increase in the synthesis and application of graphene oxide (GO), questions have emerged about its inadvertent entry into aquatic habitats and the ecological consequences associated with such exposure While several studies have addressed the acute effects of GO, knowledge on its chronic impacts across multiple trophic levels remains limited. In this study, we assessed the chronic toxicity of a well-characterized GO product using model organisms representing three trophic levels: the bioluminescent marine bacterium Aliivibrio fischeri, unicellular green algae (Chlamydomonas reinhardtii, Chlorella vulgaris, Desmodesmus subspicatus), the cyanobacterium Synechococcus elongatus, and the freshwater cladoceran Daphnia magna. Endpoints included bioluminescence inhibition in bacteria, growth inhibition in photosynthetic primary producers, and reproduction and refined physiological parameters (heart rate, feeding activity) in D. magna. Our results demonstrated clear concentration-dependent chronic effects of GO, with A. fischeri, the applied photosynthetic primary producers and D. magna exhibiting significant inhibition of bioluminescence, growth, delayed onset of reproduction, and reduced fitness parameters, respectively. Based on the collected data, a comprehensive ecotoxicological risk assessment was carried out, revealing that pristine GO may pose negligible hazard to aquatic ecosystems under environmentally relevant exposure scenarios. The outcomes clearly demonstrate the relevance of incorporating chronic and multi-trophic effects when evaluating the ecological risks of emerging nanomaterials such as GO. Full article

Background/Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor with limited therapeutic options despite multimodal treatment. Small interfering RNA (siRNA)-based therapeutics can silence tumor-promoting genes, but achieving efficient and tumor-specific delivery remains challenging. Lipid nanoparticles (LNPs) are promising siRNA carriers; however, conventional antibody conjugation can impair antigen recognition and complicate manufacturing. This study aimed to establish a modular Fc-binding peptide (FcBP)-mediated post-insertion strategy to enable PD-L1-targeted delivery of VEGF-siRNA via LNPs for GBM therapy. Methods: Preformed VEGF-siRNA-loaded LNPs were functionalized with FcBP–lipid conjugates, enabling non-covalent anchoring of anti-PD-L1 antibodies through Fc interactions. Particle characteristics were analyzed using dynamic light scattering and encapsulation efficiency assays. Targeted cellular uptake and VEGF gene silencing were evaluated in PD-L1-positive GL261 glioma cells. Anti-tumor efficacy was assessed in a subcutaneous GL261 tumor model following repeated intratumoral administration using tumor volume and bioluminescence imaging as endpoints. Results: FcBP post-insertion preserved LNP particle size (125.2 ± 1.3 nm), polydispersity, zeta potential, and siRNA encapsulation efficiency. Anti-PD-L1–FcBP-LNPs significantly enhanced cellular uptake (by ~50-fold) and VEGF silencing in PD-L1-expressing GL261 cells compared to controls. In vivo, targeted LNPs reduced tumor volume by 65% and markedly suppressed bioluminescence signals without inducing weight loss. Final tumor weight was reduced by 63% in the anti-PD-L1–FcBP–LNP group (656.9 ± 125.4 mg) compared to the VEGF-siRNA LNP group (1794.1 ± 103.7 mg). The FcBP-modified LNPs maintained antibody orientation and binding activity, enabling rapid functionalization with targeting antibodies. Conclusions: The FcBP-mediated post-insertion strategy enables site-specific, modular antibody functionalization of LNPs without compromising physicochemical integrity or antibody recognition. PD-L1-targeted VEGF-siRNA delivery demonstrated potent, selective anti-tumor effects in GBM murine models. This platform offers a versatile approach for targeted nucleic acid therapeutics and holds translational potential for treating GBM. Full article

Background: Venetoclax-based combination therapies have provided treatment options for patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy. However, venetoclax resistance is common, and for such patients, the prognosis is dismal, and treatment approaches with different mechanisms of action are urgently needed. γδ T cells are a promising candidate owing to their good safety profile and cytotoxic effects in various types of cancers but are mostly unstudied in AML. Methods: Here we used flow cytometry to profile the subtype and memory phenotype of peripheral blood γδ T cells in AML patients and investigate the feasibility of using donor-derived Vγ9Vδ2 T cells to treat AML as both a single agent and in combination with venetoclax. Additionally, we used bioluminescence imaging to examine the effect of donor-derived Vγ9Vδ2 T cells on AML xenograft models alone and in combination with venetoclax. Results: We observed that Vδ2 T cells were less abundant and the TEMRA (terminally differentiated effector memory) phenotype was more prevalent as compared with that of healthy donors, suggesting that replenishing patients with Vδ2 T cells may be an effective treatment option. We found that donor-derived Vγ9Vδ2 T cells that Vγ9Vδ2 T cells efficiently induced apoptosis in AML cells from eight cell lines and three primary cultures in an effector-to-target cell ratio-dependent manner. Moreover, Vγ9Vδ2 T cells showed potent cytotoxicity against the venetoclax-resistant OCI-AML3 cell line and remained potent in the presence of venetoclax. Treatment with Vγ9Vδ2 T cells significantly extended survival in two AML xenograft models established with the aggressive Molm-13 and the venetoclax-resistant OCI-AML3 cell lines. An additive effect of venetoclax and Vγ9Vδ2 T cells was observed in the latter model. Conclusions: Overall, these findings suggest Vγ9Vδ2 T cells as a promising “off-the-shelf” immunotherapy approach for AML patients, especially for patients with venetoclax-resistant disease. Full article

This study comprehensively evaluated the antimicrobial performance of copper ions against three bacterial species relevant to water systems: E. coli (ATCC 25922), P. aeruginosa (ATCC 27853), and S. epidermidis (ATCC 12228). Disinfection kinetics were determined at three copper concentrations (0.5, 1.5, and 3.3 mg/L) using the Gard model. E. coli exhibited the highest susceptibility, with inactivation rate constants of 0.63, 3.27, and 9.83, achieving complete inactivation at 3.3 mg/L. P. aeruginosa was the most resistant, showing values below 1.0 across all concentrations, while S. epidermidis displayed intermediate responses. Selected experiments further examined the influence of growth phase, temperature, and water chemistry. Exponential-phase cells were more sensitive than stationary-phase cultures, and higher temperatures (37 °C vs. 5 °C) significantly enhanced inactivation. Moderate bicarbonate (50 mg/L) improved bacterial removal by stabilizing soluble Cu²⁺ ions (2.60 lg reduction), whereas elevated calcium and magnesium (Ca²⁺ 100 mg/L, Mg²⁺ 50 mg/L) reduced effectiveness (≤2.10 lg reduction) through competitive interactions. In addition to culture-based methods, adenosine triphosphate (ATP) bioluminescence assays and flow cytometry (FCM) provided complementary insights, confirming early metabolic disruption and membrane damage prior to culturability loss in selected experiments. Full article

Objective: Establish an in vivo evaluation model focused on the attachment and entry stages of Hendra virus infection for protective immunity assessment. Methods: A golden hamster infection model based on recombinant Hendra-F/G pseudovirus was developed, and a luciferase luminescence assay was used to assess the optimal pseudoviral challenge in terms of route of infection, dose and detection time. The biodistribution of the pseudovirus in infected organs was evaluated using the IVIS spectral CT system. The protective effect of antibody prophylaxis was evaluated by measuring the luminescence intensity of pseudoviruses. Results: Intraperitoneal injection was identified as the optimal route of infection, and the optimal time of detection was 6 h post-challenge. Our model simulates the infection of the brain and lungs by live viruses, with the strongest infection occurring in the abdomen, especially in the intestinal organs. The dose of pseudovirus was linearly correlated with luminescence intensity. The infection model was able to differentiate the protective effect of monoclonal antibodies, with complete protection in the high-dose group. Conclusions: The recombinant Hendra-F/G pseudovirus hamster model allows the effective evaluation of prophylactic monoclonal antibodies, providing a crucial tool for studying Hendra virus infection and control strategies. Full article

Purpose: Near-infrared fluorescence-guided surgery (FGS) using cancer-specific tracers is promising for tailored gastric cancer (GC) surgery. Carcinoembryonic antigen (CEA) is a potential target due to its high expression in various digestive cancers, including GC. Materials and Methods: SGM-101, a chimeric anti-CEA monoclonal antibody conjugated with the near-infrared dye BM-104, was evaluated in GC. CEA expression was identified in GC cell lines at the mRNA and protein levels. Xenograft models (MKN-45, SNU-16, SNU-668, 85As2mLuc) were established in mice and injected with SGM-101 or PBS. Biodistribution was monitored using in vivo fluorescence imaging. Tumors were further analyzed by immunofluorescence. In a peritoneal carcinomatosis model, 85As2mLuc cells were injected intraperitoneally, and tumors were evaluated by bioluminescence and fluorescence and histology. Results: MKN-45, SNU-16, and 85As2mLuc were CEA-positive, while SNU-668 was CEA-negative. Flow cytometry confirmed CEA expression: MKN-45 (98%), SNU-16 (85.6%), SNU-668 (6.42%) and 85As2mLuc (78.4%). SGM-101 selectively targeted CEA-expressing tumors, with fluorescence peaking at 48 h, and immunofluorescence verified localization in tumor cells. In the peritoneal models, SGM-101 enabled precise detection of CEA-positive tumors. Conclusions: This study provides the first evidence for the feasibility of SGM-101 in gastric cancer, demonstrating its novelty and translational potential as a cancer-specific imaging agent for fluorescence-guided surgery. Full article

Background/Objectives: Advanced breast cancer patients may develop bone metastases, leading to severe pain, fractures, and mortality. Current treatments have limited efficacy, necessitating targeted therapy approaches. Bone metastatic breast cancer cells secrete PTHrP that promotes tumor growth and bone degradation. Previous PTH/PTHrP antagonists failed clinically due to short half-life and insufficient bone targeting. The present study evaluated the following two novel bone-targeted PTH antagonists fused to a collagen-binding domain (CBD) for enhanced bone localization: PTH(7-33)-CBD and [W2]PTH(1-33)-CBD. Methods: Intra-tibial and intra-iliac breast tumor models in mice were used to evaluate drug efficacy in reducing tumor burden and bone destruction. Results: Bioluminescent imaging, X-ray, and micro-CT analysis revealed that both drugs significantly reduced tumor burden and osteolysis compared to control, with [W2]PTH(1-33)-CBD additionally improving trabecular bone structure. Drug efficacy was confirmed in both intra-tibial and intra-iliac breast tumor models. Conclusions: These findings identify CBD-fused PTH/PTHrP antagonists as a promising therapeutic strategy for breast cancer bone metastases. Full article

Background: Donor lymphocyte infusion (DLI) is employed to enhance the graft-versus-leukemia (GvL) effect and improve remission rates following allogeneic hematopoietic cell transplantation (alloHCT). However, graft-versus-host disease (GvHD) remains a significant complication of both alloHCT and DLI. Regular exercise has been shown to reduce cancer risk, enhance treatment responses, and mitigate therapy-related toxicities. This study investigated the effects of voluntary wheel running on GvL and GvHD following DLI in a xenogeneic mouse model. Methods: Immunodeficient NSG-IL15 mice were challenged with a luciferase-expressing chronic myelogenous leukemia cell line (K562), and then they received DLI with peripheral blood mononuclear cells (PBMCs) from healthy volunteers (GvL model). Non-tumor bearing mice received DLI to model GvHD. Half of the mice in each group were then given free access to a running wheel. Tumor growth (bioluminescence), GvHD, and body weight were monitored biweekly for ~40 days. Results: In the GvHD model, exercise extended overall survival by 60% and reduced GvHD severity. In the GvL model, exercise significantly lowered tumor burden and extended tumor-free survival in both DLI and vehicle control groups by 44.5% and 37.5%, respectively, suggesting both immune-dependent and immune-independent mechanisms. RNA sequencing of bone marrow from saline-injected mice revealed that genes associated with mitochondrial function, protein synthesis, and metabolic processes were downregulated in tumors from exercised mice. Conclusions: In summary, voluntary wheel running improved DLI outcomes by enhancing GvL and reducing GvHD. These benefits may be mediated, in part, through exercise-induced metabolic reprogramming of leukemia cells. Full article

Phytoplankton–mesozooplankton interactions play a central role in shaping Black Sea food web dynamics, yet their trophic coupling has been insufficiently investigated in policy-relevant frameworks. This systematic review of 86 peer-reviewed studies (1987–2025) synthesizes research trends, limitations, and knowledge gaps in the field. The analysis reveals a clear dominance of work on plankton community structure (81%), whereas topics such as modeling and scenario analysis (7%), ecosystem assessment (7%), and bloom dynamics and seasonality (5%) remain comparatively underrepresented. Post-2020 publications indicate a promising shift toward scenario-based frameworks, gelatinous zooplankton impacts, and trait-based indicators, although functional integration remains fragmented. Keyword co-occurrence and network analyses revealed a concentration on nutrient–phytoplankton–zooplankton pathways, while other themes—such as bioluminescence and redoxcline dynamics—appeared only marginally represented in the literature we analyzed. To support ecosystem-based management under the Marine Strategy Framework Directive (MSFD), we highlight three priorities: improving NPZD-type models, using trophic efficiency metrics, and standardizing plankton indicators across the region. Strengthening the mechanistic understanding of planktonic trophic linkages is critical for improving food web assessments and adaptive marine governance in the Black Sea. Full article

Background/Objectives: Burn wound infections present significant clinical challenges due to multidrug-resistant pathogens and the limitations of traditional antimicrobials. While antimicrobial peptides (AMPs) have broad-spectrum effectiveness, their instability in wound environments limits their use. This study compares properties of AMP-decorated nanostructured lipid carriers (NLCs) to free AMPs, focusing on their dermal penetration, retention, and antimicrobial efficacy in simulated ex vivo burn wound models. Methods: AMP-decorated NLCs (smart-AMPs) were produced by electrostatic and hydrophobic surface adsorption and characterized regarding their size, zeta potential, and physical short-term stability. The distribution of AMPs within the wounds was evaluated using an ex vivo porcine ear model with various wound types. The antimicrobial efficacy was assessed by monitoring the bioluminescence of Aliivibrio fischeri as a live bacterial marker for 24 h. Results: The size and zeta potential measurements confirmed the successful formation of smart-AMPs. The dermal penetration of AMPs was influenced by the type of wound and the type of AMP formulation (free AMPs vs. smart-AMPs). In the chronically infected burn wounds, which were characterized by the formation of a biofilm in a protein-rich wound fluid, the smart-AMPs resulted in a 1.5-fold higher and deeper penetration of the AMPs, and the antimicrobial activity was 6-fold higher compared to the free AMPs. Conclusions: smart-AMPs present an innovative approach for treating chronic, biofilm-associated wounds more efficiently than the current treatment options. Full article

Given the environmental significance of the textile industry, especially the accumulation of nondegradable materials, there is extensive development of greener approaches to fabric waste management. Here, we investigated the biodegradation potential of three Streptomyces strains in model compost on polyamide (PA) and polyamide-elastane (PA-EA) as synthetic, and on cotton (CO) as natural textile materials. Weight change of the materials was followed, while Fourier-Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) were used to analyze surface changes of the materials upon biodegradation. The bioluminescence-based toxicity test employing Aliivibrio fischeri confirmed the ecological safety of the tested textiles. After 12 months, the increase of 10 and 16% weight loss, of PA-EA and PA, respectively, was observed in compost augmented with Streptomyces sp. BPS43. Additionally, a 14% increase in cotton degradation was recorded after 2 months in compost augmented with Streptomyces sp. NP10. Genome exploration of the strains was carried out for potential plastic-degrading enzymes. It highlighted BPS43 as the most versatile strain with specific amidases that show sequence identity to UMG-SP-1, UMG-SP-2, and UMG-SP-3 (polyurethane degrading enzymes identified from compost metagenome). Our results showcase the behavior of Streptomyces sp. BPS43 in the degradation of PA and PA-EA textiles in composting conditions, with enzymatic potential that could be further characterized and optimized for increased synthetic textile degradation. Full article

Background/Objectives: Paclitaxel (PTX) is widely used in the treatment of a variety of solid tumours due to its broad-spectrum anti-tumour activity, but its use in brain gliomas is limited by insufficient blood–brain tumour barrier (BBTB) penetration and systemic toxicity. The aim of this study was to develop a Solutol HS-15-based micellar nanoparticle (PSM) to enhance the brain glioma targeting of PTX and reduce toxicity. Methods: PSMs were prepared by solvent injection and characterised for particle size, encapsulation rate, haemolysis rate and in vitro release properties. A C6 in situ glioma mouse model was used to assess the brain targeting and anti-tumour effects of the PSM by in vivo imaging, tissue homogenate fluorescence analysis and bioluminescence monitoring. Meanwhile, its safety was evaluated by weight monitoring, serum biochemical indexes and histopathological analysis. Results: The particle size of PSMs was 13.45 ± 0.70 nm, with an encapsulation rate of 96.39%, and it demonstrated excellent cellular uptake. In tumour-bearing mice, PSMs significantly enhanced brain tumour targeting with a brain drug concentration 5.94 times higher than that of free PTX. Compared with Taxol, PSMs significantly inhibited tumour growth (terminal luminescence intensity <1 × 10⁶ p/s/cm²/Sr) and did not cause significant liver or kidney toxicity or body weight loss. Conclusions: PSMs achieve an efficient accumulation of brain gliomas through passive targeting and EPR effects while significantly reducing the systemic toxicity of PTX. Its simple preparation process and excellent therapeutic efficacy support its use as a potential clinically translational candidate for glioma treatment. Full article

Current osteoarthritis (OA) therapies fail to yield long-term clinical benefits, due in part to the lack of a mechanism for the targeted and confined delivery of therapeutics to OA joints. This study evaluates if M2 macrophages are effective cell vehicles for the targeted and confined delivery of therapeutic genes to OA joints. CT bioluminescence in vivo cell tracing and fluorescent microscopy reveal that intraarticularly injected M2 macrophages were recruited to and retained at inflamed synovia. The feasibility of an M2 macrophage-based adoptive gene transfer strategy for OA was assessed using IL-1Ra as the therapeutic gene in a mouse tibial plateau injury model. Mouse M2 macrophages were transduced with lentiviral vectors expressing IL-1Ra or GFP. The transduced macrophages were intraarticularly injected into injured joints at 7 days post-injury and OA progression was monitored with plasma COMP and histology at 4 weeks. The IL-1Ra-expressing M2 macrophage treatment reduced plasma COMP, increased the area and width of the articular cartilage layer, decreased synovium thickness, and reduced the OARSI OA score without affecting the osteophyte maturity and meniscus scores when compared to the GFP-expressing M2 macrophage-treated or PBS-treated controls. When the treatment was given at 5 weeks post-injury, at which time OA should have developed, the IL-1Ra-M2 macrophage treatment also reduced plasma COMP, had a greater articular cartilage area and width, decreased synovial thickness, and reduced the OARSI OA score without an effect on the meniscus and osteophyte maturity scores at 8 weeks post-injury. In conclusion, the IL-1Ra-M2 macrophage treatment, given before or after OA was developed, delayed OA progression, indicating that the M2 macrophage-based adoptive gene transfer strategy for OA is tenable. Full article

Background: To overcome the limitations of conventional CRC (colorectal cancer) mouse models in replicating metastasis and enabling efficient therapeutic evaluation, we developed a novel implantation method using tissue adhesive to establish reproducible orthotopic and metastatic tumors. Conventional models using injection or suturing techniques often suffer from technical complexity, inconsistent tumor establishment, and limited metastatic reliability. Methods: We developed and validated a novel orthotopic and metastatic CRC model utilizing tissue adhesive for tumor transplantation. Uniform tumor fragments derived from bioluminescent HCT116/Luc xenografts were affixed to the cecum of nude mice. Tumor growth and metastasis were monitored through bioluminescence imaging and confirmed by the results of histological analysis of metastatic lesions. The model’s utility for therapeutic testing was evaluated using MK801, an NMDA receptor antagonist. Results: The biological-based model demonstrated rapid and reproducible tumor implantation (<5 min), consistent primary tumor growth, and robust metastasis to the liver and lungs. The biological-based approach achieved 80% tumor engraftment (4/5), with consistent metastasis to the liver and lungs in all mice, compared with lower and variable metastasis rates in injection (0%, 0/5) and suturing (20%, 1/5) methods. MK801 treatment significantly suppressed both primary tumor growth and metastasis, validating the model’s suitability for preclinical drug evaluation. Conclusions: By enabling rapid, reproducible, and spontaneous formation of metastatic lesions using a minimally invasive tissue adhesive technique, our model represents a significant methodological advancement that supports high-throughput therapeutic screening and bridges the gap between experimental modeling and clinical relevance in colorectal cancer research. Full article