Search Results (1,134)

Background: Recombinant human arginase (rhArg) has been proven to exhibit an anticancer effect via arginine starvation. To further improve the efficacy of rhArg, we examined the feasibility of a combination strategy with Bcl-2 inhibitors (ABT263 and ABT199) or an antidiabetic drug (metformin) and investigated the mechanistic basis for these strategies. Methods: The combination effects were evaluated in a panel of human cancer cell lines modeling pancreatic ductal carcinoma (PDAC), triple-negative breast cancer (TNBC), colorectal cancer (CRC) and glioblastoma (GBM). Western blot analysis was used to evaluate the expression of apoptotic and cell cycle markers. MTT assay was used to evaluate the combination efficacy. Flow cytometric assays were used to investigate the apoptotic and cell cycle effects. Results: The combination of rhArg with sublethal doses of ABT263 significantly induced dose-dependent apoptosis, with elevated expression of apoptotic markers and a CI of 0.47 in U251. The combination inhibited CDK2 and cyclin A expression, indicating that the observed synergy also resulted from cell cycle arrest. We also found that rhArg + metformin was synergistic in a time-dependent manner. Compared to other amino acid depletion agents, rhArg + ABT263 was the most favorable combination pair. Conclusions: The combination of rhArg and ABT263 enhanced apoptosis and cell cycle arrest, demonstrating a potential broad-spectrum antitumor strategy. Full article

Biofuel cells (BFCs) generate electricity by converting chemical energy into electrical energy using biological systems. Saccharomyces cerevisiae (yeast) is an attractive biocatalyst for BFCs due to its robustness, low cost, and metabolic versatility; however, electron transfer from the intracellular reactions to the electrode is limited by the cell membrane. Nystatin is an antifungal antibiotic that increases the permeability of fungal membranes. We hypothesized that sub-lethal nystatin treatment could enhance mediator-assisted electron transfer without compromising cell viability. In this work, yeast was treated with nystatin during cultivation at concentrations of up to 6 µg/mL and combined with a dual-mediator system consisting of a lipophilic mediator (9,10-phenanthrenequinone, PQ) and a hydrophilic mediator (potassium ferricyanide). Scanning electrochemical microscopy revealed that the dual-mediator system increased local current responses by approximately fivefold compared to a single mediator (from ~11 pA to ~59 pA), and that nystatin-treated yeast exhibited higher local electrochemical activity than untreated yeast (maximum currents of ~0.476 nA versus ~0.303 nA). Microbial fuel cell measurements showed that nystatin treatment increased the maximum power density from approximately 0.58 mW/m² to approximately 0.62 mW/m² under identical conditions. Nystatin concentrations between 4 and 5 µg/mL maintain yeast viability at near-control levels, while higher concentrations cause a decrease in viability. These results demonstrate that controlled, sub-lethal membrane permeabilization combined with a dual-mediator strategy can enhance electron transfer in yeast-based biofuel cells. Full article

Implementing mating disruption (MD) programs to manage codling moth (CM), Cydia pomonella (L.), should be based on knowledge of how effectively each program disrupts female mating. A recent survey of 142 pome fruit orchards under MD in Washington State and Oregon found that, on average, about half of the CM females caught in traps baited with a kairomone-based lure were mated. However, significantly lower proportions of mated females were sampled when the intensity of the MD program was increased. A standardized protocol that could reduce the large inter-orchard variability was developed, involving weekly releases of sterilized CM adults. Eleven trials were conducted in 2023 and 2024 across 82 orchards treated with 20 MD programs. The intensive MD programs were significantly more effective in reducing mating of both wild and sterile CM females. Three advantages of using sterile moths to assess CM MD were identified: (i) it minimized the impact of wild immigrant females or individuals previously exposed to sublethal spray residues; (ii) it allowed greater numbers of females to be dissected, thus increasing the precision of the mean value; and (iii) it and allowed the collection of sufficient sampling data (>5 CM females per site) from 30% more orchards than relying on wild moth catch. Full article

Nitrite pollution in aquatic environments, often driven by human activity, can disrupt fish physiology. Nitrite is absorbed by freshwater fish through their gills, leading to internal accumulation and interference with nitric oxide (NO) signaling, redox state, and the oxygen-carrying capacity of blood. The effects of nitrite are concentration-dependent. Although moderate environmental nitrite levels have little impact on oxygen transport, they may still interfere with NO homeostasis and cellular metabolism. We report the effects of 72 h of exposure to 10 μM nitrite on adult zebrafish blood’s O₂-carrying capacity and on muscle mitochondrial activity, metabolism, and redox state. The results show that this environmentally relevant but moderate concentration of nitrite leads to decreases in fish routine oxygen consumption (rMO₂) and spontaneous activity, an increase in blood nitrosyl hemoglobin (HbNO), indicating increased NO production in the blood, accumulation of nitrite in muscle tissue, oxidative stress, and changes in muscle aerobic capacity linked to a rise in mitochondrial efficiency. Parallel to these effects, increases in antioxidant capacity, arginase activity, and urea and lactate levels were observed. Globally, these results are consistent with altered NO homeostasis in the fish body induced by nitrite stress. Full article

Coelomactra antiquata, a marine bivalve of high nutritional and economic value, lacks comprehensive data on its toxic responses and adaptive mechanisms to ammonia nitrogen. This study integrated histophysiology, transcriptomics, and metabolomics to investigate its ammonia tolerance and molecular mechanisms, determining a 48 h LC₅₀ of 99.06 mg/L and a sublethal concentration of 9.91 mg/L. After 48 h of sublethal ammonia stress, SOD, CAT, GLDH, and GS activities in gill and hepatopancreas significantly increased, with notable changes in MDA, Gln, and urea contents, confirming disruption of antioxidant defense and nitrogen metabolism homeostasis. Tissue sections revealed irreversible histopathological damage to key tissues. Omics analyses identified 7823 differentially expressed genes (DEGs) and 737 differentially expressed metabolites (DEMs) in hepatopancreas. DEGs were enriched in metabolic pathways and multiple immune-related signaling pathways (e.g., NF-kappa B, RIG-I-like receptor), while DEMs were primarily involved in processes such as protein digestion/absorption, aminoacyl-tRNA biosynthesis, and amino acid metabolism. Research data indicate that ammonia nitrogen stress primarily regulates the antioxidant function and nitrogen metabolism homeostasis of C. antiquata by activating multiple immune- and metabolism-related pathways. This first systematic multi-omics study elucidates C. antiquata’s tolerance to ammonia nitrogen and its molecular responses, filling a gap in environmental toxicology research for sustainable aquaculture and genomic studies. Full article

The need for contrasting Healthcare-Associated Infections requires the promotion and support of alternative disinfection techniques. Due to the antimicrobial potential of UV, devices equipped with UVC, UVB and UVA lamps or LEDs have been developed in recent years for domestic, everyday use. In this study, four bacterial strains (S. aureus, E. faecalis, E. coli, and P. aeruginosa) were exposed to different doses of near-UVA radiation at 405 nm, with an average irradiance of 21 mW/cm², using an experimental multi-LED device. Bacterial suspensions were irradiated under both sub-lethal and non-sub-lethal stress conditions. When using only near-UVA light, the highest abatement effect was observed on P. aeruginosa (2.4 log₁₀). Treatment with osmotic stress, in combination with light irradiation, was effective on all bacterial strains (mean abatement of 2.76, 5.46, 5.31, and 1.5 log₁₀ on E. coli, E. faecalis, P. aeruginosa, and S. aureus, respectively). In heat stress conditions at 4 °C, P. aeruginosa and S. aureus species were the most susceptible (2.76 and 5.5 log₁₀), whereas at 45 °C all species, except E. faecalis (0.58 log₁₀), achieved significant reduction. The addition of exogenous photosensitive porphyrins produced a reduction in total concentrations from the lowest doses for S. aureus and P. aeruginosa, while for E. coli and E. faecalis, the reductions did not exceed 1 log₁₀ abatement. Near-UVA radiation at 405 nm has a high disinfectant potential when combined with certain sub-lethal stress conditions. The most significant germicidal effect was achieved with the use of exogenous porphyrins in S. aureus and P. aeruginosa species. This study opens perspectives on the possible future application of near-UVA radiation in disinfection in order to limit the spread of healthcare-related infections. Full article

Landfills represent increasingly common anthropogenic habitats that provide food resources but also expose wildlife to complex chemical mixtures. White Storks (Ciconia ciconia) have recently expanded breeding near such sites, yet little is known about the physiological consequences of landfill dependence across time. In 2025, we assessed biomarker responses in White Stork (Ciconia ciconia) nestlings from the Jakuševec landfill (Zagreb, Croatia), a post-remediated site still in partial operation, three years after the initial studies conducted in 2021 and 2022. Activities of acetylcholinesterase (AChE), carboxylesterase (CES), glutathione S-transferase (GST) and glutathione reductase (GR), as well as levels of reduced glutathione (GSH) and reactive oxygen species (ROS), were quantified in extracellular (plasma) and intracellular (post-mitochondrial S9) blood fractions. Neurotoxicity biomarkers (AChE, CES) showed small increases in 2022, followed by significant declines in 2025, indicating potential changes in exposure to neuroactive compounds. Oxidative-stress biomarkers displayed contrasting patterns: GST and GR decreased progressively, whereas ROS rose and GSH shifted in opposite directions between fractions, together suggesting rising oxidative challenge and altered redox balance. The combined biomarker response suggests continuing low-level exposure to neurotoxic and redox-active compounds despite landfill remediation. Our findings highlight that urban landfills, even in post-closure phases, remain physiologically active systems influencing wildlife health and should be incorporated into long-term ecotoxicological and conservation monitoring frameworks. While independent long-term monitoring shows that the Jakuševec White Stork colony has continued to grow over the past decade, the physiological responses detected in nestlings highlight the importance of assessing how chronic low-level exposure might influence population health in the long term. Full article

Fungicides play a critical role in crop protection, yet their potential threats to pollinator remain a concern. This study investigated the sublethal effects of a commercial fungicide, Chunmanchun^® (a suspension-emulsion of 7% propiconazole and 28% carbendazim), on cognitive functions of the honey bee (Apis mellifera). Using the proboscis extension reflex (PER) assay, we evaluated sucrose sensitivity and olfactory learning and memory in workers exposed to the recommended field concentration (PC), along with sublethal (LD₁₀) and semi-lethal (LD₅₀) concentrations. Fungicide exposure significantly reduced sucrose sensitivity across all concentrations tested (0.1%, 1%, and 3%), with the strongest reductions occurring at the LD₁₀ and LD₅₀ levels. While olfactory associative learning was not significantly impaired, memory retention was adversely affected. Bees in the LD₅₀ group showed significantly reduced PER rates at both1 h and 6 h post-training, and LD₁₀ and LD₅₀ groups exhibited significant memory deficits by 1 h and 6 h relative to the control. These results demonstrate that Chunmanchun^® impairs both sucrose responsiveness and olfactory memory in honey bees, which may impair foraging efficiency and ultimately affect colony performance. This study highlights a potential ecological risk posed by this fungicide to pollinators in agricultural environments. Full article

Background/Objectives: Colistin (polymyxin E) has re-emerged as a last-hope treatment against MDR Gram-negative pathogens due to the development of extensively drug-resistant Gram-negative bacteria. Unfortunately, rapid global resistance towards colistin has emerged, which represents a major public health concern. In this context (CBD), a lipophilic molecule derived from Cannabis sativa, exhibits antimicrobial activity mainly against Gram-positive bacteria but is generally ineffective against Gram-negative species. However, synergistic antibacterial activity between CBD and polymyxin B has been reported. The objective of this work is to analyze the colistin–CBD synergy against clinically relevant Gram-negative isolates displaying diverse mechanisms of colistin resistance and to explore the basis of the possible mechanism of action involved in the first steps of this synergy. Methods: Microbiological assays, minimal inhibitory concentration, cell culture, synergy tests by checker board and time kill, biofilm inhibition evaluation by crystal violet and MTT, SEM (scanning electron microscopy), molecules interaction analysis by nuclear magnetic resonance (NMR). Results: The colistin–CBD combination displayed synergy in colistin resistant Gram-negative bacteria and also disrupted preformed biofilms and killed bacteria within them. Time-kill assays revealed rapid bactericidal activity and SEM showed mild surface alterations on bacterial outer membranes after sublethal colistin monotherapy. Furthermore, a series of sequential treatment assays on colistin-resistant Escherichia coli showed that simultaneous exposure to both compounds was required for activity, as introducing a washing step between treatments abolished the antibacterial effect. In order to obtain deeper insight into this mechanism, NMR analyses were performed, revealing specific molecular interactions between CBD and colistin molecules. Conclusions: These results provide evidence for the first time that both molecules engage through a specific and structurally meaningful interaction and only display synergy when acting together on colistin-resistant bacteria. Full article

Background/Objectives: The current strategy for seasonal influenza prophylaxis relies on updating the vaccine components annually to account for the rapid antigenic drift of viruses and the low cross-protective efficacy of available vaccines. Mutant influenza viruses with truncated or deleted NS1 protein are known to stimulate cross-specific T-cell immune response and provide protection against heterosubtypic influenza A and B viruses. Methods: We generated NS1ΔC influenza A and B viruses with C-terminal NS1 deletions by reverse genetics. In a mouse model, we assessed the safety and immunogenicity of the B/Lee/NS1ΔC strain upon intranasal administration, as well as the mechanism of its cross-protective efficacy against sublethal B/Victoria and B/Yamagata challenges. We then investigated the potential of the intranasal Flu/NS1ΔC vaccine–a trivalent formulation of NS1ΔC A/H1N1, A/H3N2, and B influenza viruses–to protect mice from lethal influenza infection with homologous, heterologous, and antigenically drifted influenza A and B viruses. Results: Intranasal immunization with the B/Lee/NS1ΔC strain was safe in mice. It activated cross-specific T-cell responses in the lungs and protected animals against heterologous challenge by reducing viral load, inflammation, and lung pathology. Immunization with the trivalent Flu/NS1ΔC vaccine formulation improved survival and reduced weight loss and viral load upon challenge with A/H1N1pdm, A/H2N2, A/H5N1, and B/Victoria viruses. Conclusions: The trivalent intranasal Flu/NS1ΔC influenza vaccine is a promising tool to improve seasonal influenza protection and preparedness for an influenza pandemic. Full article

Oil pollution effects on mangroves may be categorised as lethal (acute) and sublethal (chronic). Lethal effects usually occur at high oil dosage, which smothers and kills the entire root system and causes mass mortality. Sublethal effects occur when oil enters with tidal inundation or becomes trapped in sediments, resulting in prolonged deleterious effects that do not cause mortality. Long-term sublethal effects, however, are poorly understood. This review summarises the current information on the sublethal effects of oil pollution on mangroves. It begins by examining the characteristics of oil and then evaluates the effects of oil on propagules, roots, and leaves, as well as the underlying ecophysiological mechanisms of toxicity. Within cells, PAHs target organelles responsible for cell metabolism and energy relations, including the nucleus, mitochondria, and chloroplasts. Oil disorganises and disintegrates the lipid components of membranes, increasing their permeability. Responses of mangroves to oil include leaf senescence, defoliation and reductions in photosynthesis and biomass. Oil also decreases reproductive capacity, inhibits germination, induces mutations, and causes the development of anomalous growth forms, as well as oxidative stress and mortality. Abnormal root development at the lower portions of the stem and chlorophyll-deficient propagules are suggested as biological indicators of oil contamination in mangroves. Full article

Myzus persicae is a worldwide insect pest with high resistance to many traditional insecticides. Cycloxaprid, a novel cis-configuration neonicotinoid insecticide, is effective in controlling neonicotinoid-resistant insect pests. Lethal and sublethal effects of cycloxaprid on M. persicae were conducted in this study. Results showed that cycloxaprid had higher toxicity to the laboratory and field resistant M. persicae than imidacloprid. Because of the resistance, imidacloprid showed lower control efficacy (<60%) against M. persicae, which falls short of the efficacy required for practical agricultural management. However, cycloxaprid exhibited higher control efficacies (>84.79%) against M. persicae in the field. In addition, in order to quantify the sublethal impacts of cycloxaprid, we conducted a life table analysis on M. persicae. When resistant M. persicae was treated with LC₂₅ of cycloxaprid or imidacloprid, the longevity and fecundity of F₁ adults were significantly decreased. Meanwhile, the intrinsic rate of increase (r_m), finite rate of increase (λ) and net reproduction rate (R_i) of F1 generation M. persicae were reduced in cycloxaprid and imidacloprid treatments. Therefore, cycloxaprid shows high potential as a candidate insecticide for managing imidacloprid-resistant M. persicae. Importantly, our laboratory data indicate that exposure to its low sublethal concentration (LC₂₅) inhibits population growth parameters, suggesting a low risk of inducing pest resurgence under such conditions. Full article

Neonicotinoid insecticides were initially hailed as safer alternatives to organochlorine and organophosphate pesticides due to their perceived lower toxicity to non-target organisms. However, it has been recently discovered that sublethal exposure to neonicotinoids negatively affects beneficial arthropods that are essential for a functional ecosystem. These beneficial arthropods include pollinators, biological control agents, and decomposers. This review synthesizes current research on the physiological, behavioral, and reproductive consequences of neonicotinoids on non-target arthropods and their broader ecological impact. The chemical and physical properties of neonicotinoids raise concerns about long-term ecological consequences of neonicotinoid use because these chemicals are persistent in plants and soil, which contributes to prolonged exposure risks for organisms. Sublethal doses of neonicotinoids can disrupt the ecological services provided by these organisms by impairing essential biological processes including motor function, odor detection, development, and reproduction in insects, while also altering behavior such as foraging, mating, and nesting. Furthermore, neonicotinoid exposure can alter community structure, disrupting trophic interactions and food web stability. Recognizing the sublethal impacts of neonicotinoids is critical for the development of more sustainable pest management strategies. It is imperative that future research investigates the underlying mechanisms of sublethal toxicity and identifies safer, more effective approaches to neonicotinoid-based pest control to mitigate adverse ecological effects. Incorporating this knowledge into future environmental risk assessments will be essential for protecting biodiversity and maintaining ecosystem functionality. Full article

Background: Oxidative stress is a key contributor to many chronic diseases. Natural biocompounds with antioxidant activity are of growing therapeutic interest. Brassica macrocarpa, a plant from the Brassicaceae family, has shown in vitro safety and antioxidant potential due to its rich content of glucosinolates and phenolics. However, in vivo, its effects remain poorly characterized. This study aimed to evaluate the in vivo safety and biological effects of Brassica macrocarpa leaf extract in zebrafish embryos and to assess its potential to counteract copper sulphate (CuSO₄)-induced oxidative stress. Methods: Zebrafish embryos were exposed to Brassica macrocarpa extract at concentrations from 125 to 2000 µg/mL. Embryonic mortality and malformations were monitored daily to determine sub-lethal concentrations (125–500 µg/mL) for further behavioural and biochemical analysis. Antioxidant properties were tested in a CuSO₄-induced oxidative stress model. Results: No teratogenic effects were observed over 96 h. Larvae showed normal swimming and no behavioural changes. Pre-treatment with the extract significantly reduced CuSO₄-induced ROS and NO production, modulated antioxidant enzyme (SOD, CAT) activity, and lowered lipid peroxidation and protein oxidation, slightly affecting DNA damage. Conclusions: Brassica macrocarpa extract in vivo appears safe at sub-lethal doses and shows promising antioxidant effects, suggesting its potential role in managing oxidative stress-related conditions. Full article

Caffeine (CAF), a prevalent psychoactive compound, has been identified as a significant environmental pollutant in freshwater ecosystems. This study investigates the behavioral and physiological effects of CAF at environmentally relevant concentrations (0, 5, 30, and 50 µg/L) on the freshwater snail Physella acuta, with a focus on both adult and embryonic responses. Adult snails were evaluated for alterations in speed, exploration, overall activity levels, and feeding behaviors, while embryos were assessed for heart rate and developmental changes. The study encompassed both short-term (24 h) and mid-term (7 days) exposure periods. Low CAF concentrations (5 and 30 µg/L) were found to enhance adult movement and exploratory behavior in the short term, whereas prolonged exposure resulted in a decline in these behaviors. A high CAF concentration (50 µg/L) consistently diminished movement and feeding in adults. Embryos exhibited a dose-dependent increase in heart rate and manifested malformations at elevated concentrations. These findings provide insights into the impact of CAF on freshwater invertebrates and contribute valuable data for ecological risk assessment. Full article