搜索结果：Veterinary and human toxicology

Transmission of extended-spectrum β-lactamases-producing (ESBL) Escherichia coli from meat and meat by-products to humans has emerged as a major public health issue, requiring a One Health framework to address this menace. Hence, we investigated the phylotypes, antimicrobial resistance profiles, and virulotypes of E. coli isolates from chicken meat, beef burger, and human stool samples, besides investigating the in vitro antimicrobial and antivirulence efficacies of liposomal cinnamon, oregano, and clove essential oils (LCOC). A total of 90 isolates (28.1%) were phenotypically and molecularly identified as E. coli, and they were classified into four phylogenetic groups: B1, B2, A, and D (40, 35.6, 14.4, and 10%, respectively). The majority of the isolates were multidrug-resistant (MDR) (97.8%), with remarkable resistance against ampicillin, tetracycline, and cefotaxime (95.6, 84.4, and 81.1%, respectively). The blaTEM, tetA, aadA1, and blaCTX-M were the most prevalent resistance genes (96.7, 85.6, 81.1, and 81.1%, respectively). Virulotyping revealed that 70% of the isolates were multi-virulent, with iroN being the most prevalent one (92.2%). LCOC demonstrated in vitro antibacterial and antivirulence properties via inhibiting the growth of MDR, multi-virulent, and ESBL meat E. coli isolates and downregulating the expression of their investigated virulence genes. Concisely, the observed 28.1% prevalence of ESBL-producing E. coli indicates a notable public health concern associated with meat contamination. Our findings demonstrate that LCOC exhibited antimicrobial activity against the tested E. coli isolates and may help reduce their antibiotic resistance and virulence potential.

Benzimidazoles are an important class of anthelmintics used to control parasitic infections in food-producing animals. However, these drugs can cause toxicological effects such as embryotoxicity, teratogenicity, polyploidy, and gastrointestinal disturbances. Monitoring benzimidazole residues in animal-derived foods is essential for human health. This review outlines the structural characteristics, classification, and toxicity of benzimidazole veterinary drugs, with a focus on their effects on animals, the environment, and humans. It discusses recent advancements in sample preparation and detection techniques, highlighting novel adsorbents like molecularly imprinted polymers and metal-organic network composites for enhanced selectivity and adsorption capacity. Developments in chromatographic methods, ELISA, and sensor technologies for benzimidazole detection are also reviewed, showcasing improvements in analytical performance, including low detection limits and reliable recoveries in complex food matrices. This work offers insights into future challenges and opportunities in benzimidazole research to guide detection strategies and ensure food safety.

The burden of nephrotoxicity and ototoxicity consequences caused by gentamicin warrants preventive therapeutic measures. Our aim was to evaluate combined and potentially synergistic effects of rosuvastatin and curcumin, both possessing anti-inflammatory and antioxidant properties, compared to their monotherapies in a gentamicin-induced model of nephrotoxicity and ototoxicity. In a randomized, controlled study, 36 male Wistar rats were allocated to six groups and treated for 5 days: negative control group received solvent, model group gentamicin (100 mg/kg, intraperitoneally), treatment groups gentamicin and via orogastric tube either standard-dose rosuvastatin (5 mg/day), reduced-dose rosuvastatin (1.25 mg/day), curcumin (100 mg/kg), or combination of reduced-dose rosuvastatin and curcumin. Human rosuvastatin doses were converted to rat doses using the conversion factor of 6.2. Functional outcomes evaluated by Preyer pinna reflex for hearing and a vestibular battery test were complemented by renal and cochlear histology, biochemical biomarkers of injury, inflammation, and oxidative stress. Gentamicin induced proximal tubular necrosis and cochlear and vestibular damage. Compared to monotherapies, combination therapy significantly preserved renal architecture, improved renal biomarkers, reduced early inflammatory biomarkers, preserved cochlear architecture and drove vestibular protection. It also alleviated gentamicin-induced cardiotoxicity. Rosuvastatin provided stronger auditory protection, with reduced-dose rosuvastatin superior to standard-dose in preserving vestibular function. Bliss independence modelling showed that combined therapy synergistically inhibited kidney injury and inflammation. In conclusion, the combination of reduced-dose rosuvastatin and curcumin outperforms both monotherapies in alleviating gentamicin-induced nephrotoxicity, audiotoxicity and vestibulotoxicity, whilst synergistically attenuating nephrotoxicity and early-phase inflammation in rats. These findings highlight promising preventive strategies against aminoglycoside nephrotoxicity and ototoxicity.

Anesthetics are widely employed in aquaculture and in research environments utilizing fish as experimental models, with the aim of mitigating stress and hypermotility during handling procedures. Among the most commonly used anesthetic agents, eugenol stands out for its suitability across multiple species, enabling safer handling and transportation while minimizing physiological impact on the animals. For the experimental procedure, three oil mixtures were prepared in a 1:1 ratio. The first contained 50% eugenol and 50% Nepeta cataria essential oil (ENCO); the second mixture was 50% eugenol and 50% corn oil (Zea mays) (ECO); and the third was 50% Nepeta cataria essential oil and 50% corn oil (NCCO). The present study proposes a behavioral and electrophysiological assessment of Colossoma macropomum subjected to immersion baths containing different concentrations of Nepeta cataria L. 50% and eugenol 50%, in addition to investigating the underlying components of the synergism and the mechanism of action of eugenol. A total of 288 juvenile specimens, of mixed sex, with a mean body mass of 25.34 ± 3.2 g, were used. Experiment 1: assessed the synergistic potentiation between the compounds, based on latency times for anesthetic induction and recovery. Experiment 2: performed electrophysiological analyses of muscle (EMG) and cardiac (ECG) functions. Experiment 3: evaluated the influence of flumazenil on the activation of the anesthetic agents. Evaluations were conducted during 10-minute immersion baths at concentrations of 30 µL·L⁻¹, 35 µL·L⁻¹, 40 µL·L⁻¹, 45 µL·L⁻¹, and 50 µL·L⁻¹. The combination of Nepeta cataria essential oil and eugenol promotes good muscle relaxation and minor alterations in the cardiovascular system, promoting easily reversible bradycardia. The findings indicate that the combination of Nepeta cataria essential oil and eugenol constitutes a promising and safe alternative, due to the synergistic reduction in induction time and the maintenance of cardiac safety, which allowed for a reduction in the concentration required without compromising the maintenance of the anesthetic plane. Furthermore, flumazenil was found to exert a significant influence on both the induction process and the recovery phase of anesthesia.

This study aimed to investigate the wound-healing potential of syringic acid (SA) through integrated in silico and in vitro approaches using human dermal fibroblasts (HDFs). Network pharmacology analysis identified myeloperoxidase (MPO), a key enzyme involved in oxidative stress and inflammation, as a primary target of SA. Computational predictions also indicated favorable pharmacokinetic and ADMET properties. In vitro experiments were conducted using SA at concentrations of 50–400 µM. Cell viability was assessed by MTT and LDH assays, while antioxidant and inflammatory responses were evaluated by measuring SOD, CAT, MDA, TNF-α, IL-1β, TGF-β, iNOS, and hydroxyproline levels. SA treatment significantly enhanced fibroblast viability and exhibited strong antioxidant effects, as demonstrated by increased SOD and CAT activities and reduced MDA levels. Additionally, SA suppressed pro-inflammatory mediators (TNF-α, IL-1β, and iNOS) while upregulating TGF-β expression. Importantly, SA promoted collagen synthesis, evidenced by increased hydroxyproline content. Among the tested doses, 100–200 µM showed the most pronounced effects. Overall, these findings demonstrate that SA facilitates wound healing by improving cellular viability, reducing oxidative stress and inflammation, and enhancing collagen production. This study highlights SA as a promising multi-target therapeutic candidate for wound repair, although further in vivo and safety studies are required to support its clinical application.

To use liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis to quantify kratom alkaloids and metabolites in the urine of healthy dogs following a single oral dose of an encapsulated kratom extract and evaluate the accuracy of an over-the-counter (OTC) human kratom urine test for identifying the presence of kratom alkaloids and metabolites in canine urine. Urine samples were collected from 8 healthy female Beagles following a single oral dose of an encapsulated kratom extract (8 mg) every 4 hours for 24 hours. Urine concentrations of kratom alkaloids and metabolites were measured using LC-MS-MS analysis. Urine samples were tested with an OTC human kratom urine test for identification of mitragynine and/or 7-hydroxymitragynine. In this small cohort of dogs, the OTC human kratom urine test demonstrated 100% sensitivity (6 of 6; 95% CI, 60.97% to 100.00%) and 100% specificity (7 of 7; 95% CI, 64.57% to 100.00%) for identifying kratom alkaloids and/or metabolites. Kratom metabolite 7-hydroxymitragynine had higher urine concentrations compared to the parent alkaloid mitragynine. Kratom is primarily excreted as metabolites in canine urine following oral administration of a single dose. Although these results are limited by the small sample size and wide CIs, the OTC human kratom urine test reliably detected kratom metabolites in canine urine when compared with LC-MS-MS. The results of this study provide a better understanding of kratom elimination in dogs and support the potential utility of an OTC kratom urine test as a diagnostic tool for suspected kratom exposure; however, larger studies are needed to validate diagnostic performance.

Information on childhood cancer burden is crucial for effective cancer policy planning. Unfortunately, observed paediatric cancer data are not available in every country, and previous global burden estimates have not discretely reported several common cancers of childhood. We aimed to inform efforts to address childhood cancer burden globally by analysing results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, which now include nine additional cancer causes compared with previous GBD analyses. GBD 2023 data sources for cancer estimation included population-based cancer registries, vital registration systems, and verbal autopsies. For childhood cancers (defined as those occurring at ages 0-19 years), mortality was estimated using cancer-specific ensemble models and incidence was estimated using mortality estimates and modelled mortality-to-incidence ratios (MIRs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the standard life expectancy at the age of death. Prevalence was estimated using survival estimates modelled from MIRs and multiplied by sequelae-specific disability weights to estimate years lived with disability (YLDs). Disability-adjusted life-years (DALYs) were estimated as the sum of YLLs and YLDs. Estimates are presented globally and by geographical and resource groupings, and all estimates are presented with 95% uncertainty intervals (UIs). Globally, in 2023, there were an estimated 377 000 incident childhood cancer cases (95% UI 288 000-489 000), 144 000 deaths (131 000-162 000), and 11·7 million (10·7-13·2) DALYs due to childhood cancer. Deaths due to childhood cancer decreased by 27·0% (15·5-36·1) globally, from 197 000 (173 000-218 000) in 1990, but increased in the WHO African region by 55·6% (25·5-92·4), from 31 500 (24 900-38 500) to 49 000 (42 600-58 200) between 1990 and 2023. In 2023, age-standardised YLLs due to childhood cancer were inversely correlated with country-level Socio-demographic Index. Childhood cancer was the eighth-leading cause of childhood deaths and the ninth-leading cause of DALYs among all cancers in 2023. The percentage of DALYs due to uncategorised childhood cancers was reduced from 26·5% (26·5-26·5) in GBD 2017 to 10·5% (8·1-13·1) with the addition of the nine new cancer causes. Target cancers for the WHO Global Initiative for Childhood Cancer (GICC) comprised 47·3% (42·2-52·0) of global childhood cancer deaths in 2023. Global childhood cancer burden remains a substantial contributor to global childhood disease and cancer burden and is disproportionately weighted towards resource-limited settings. The estimation of additional cancer types relevant in childhood provides a step towards alignment with WHO GICC targets. Efforts to decrease global childhood cancer burden should focus on addressing the inequities in burden worldwide and support comprehensive improvements along the childhood cancer diagnosis and care continuum. St Jude Children's Research Hospital, Gates Foundation, and St Baldrick's Foundation.

Endocrine disruptors, ubiquitous in terrestrial and aquatic environments, have come under increased public and scientific scrutiny and are classified as substances of great concern for human health and the environment. The main objective of which is to determine the potential role of sodium fluoride (NaF) on rainbow trout health, with a particular interest in the thyroid hormone system, the immune system, and the development and behavior in early life stages. Rainbow trout (Oncorhynchus mykiss) embryos (265DD) were exposed for 15 days to NaF at 0, 0.5, 1, 5, 8 and 15 mg/L of F-. After the first 15 day-exposure, larvae were divided into three batches (1) exposed to NaF for further 8 days at the same concentrations, (2) infected with the Infectious Hematopoietic Necrosis virus, or (3) held in clean water. Fish were monitored daily to follow their development, morphology and behavior and sampled after 15 or 23 days of exposure, with and without viral infection, to evaluate effects on the THS (eye development, thyroid) and their capacity of resistance to IHNV. Results show impaired growth (decrease in size and an increase in the rate of abnormalities rate) and significative behavior impact at 15 mg/L of F- with a decrease of activity (speed, and light stress reaction). 5 mg/L of F- caused delayed hatching, a decrease in virus-related mortality, an increase of thyroid follicles number, and increased photoreceptor layer thickness. Further analyses will determine the immunotoxicity of this potential ED by analyzing gene activity and blood parameters in older fish.

Phenethylamine (PEA) and alkylamine (AA) analogues are a prominent group of pre-workout food supplement ingredients. They are structurally related to the stimulant amphetamine and to the endogenous catecholamines noradrenaline and dopamine, implying potential cardiovascular and psychological effects. This study systematically investigated the inhibitory potential of 12 PEAs and 4 AAs identified in pre-workout supplements on the human dopamine transporter (hDAT), human noradrenaline transporter (hNET) and human serotonin transporter (hSERT) that are stably overexpressed in HEK 293 cells. All PEAs and AAs tested, except DMAE, inhibited substrate uptake by one or more monoamine transporters. Overall, the substances displayed the highest potency and efficacy at hNET, followed by hDAT and with considerably weaker effects on hSERT. At hNET, potency values (IC50) ranged from 0.5 µM to 123 µM, with maximal inhibition (Emax) ranging from -59.2% to -120%. Inhibition of substrate uptake by hDAT occurred with IC50 values between 4.0 and 95.8 µM and Emax values between -66.8% and -135%. For hSERT 50% inhibition was observed at concentrations ranging from 2.6 µM to 131 µM, with maximal effect between 85.3% and -64.8%. These findings indicate a potential for sympathetic activation and behavioral rewarding and reinforcing effects. Notably, the in vitro potency and efficacy of several PEAs and AAs were comparable to those of the well-known illicit stimulants amphetamine and cocaine. Together, these findings highlight the urgent need to further characterize pharmacokinetic and pharmacodynamic properties of these pre-workout supplement ingredients to support robust risk assessment and informed regulatory decision-making regarding the safety of pre-workout supplement ingredients.

Prolonged detection of rhinovirus (RV) in secretions after a typical cold and asymptomatic shedding are frequently reported. Although RV has been detected in human hypertrophic tonsils, its replicative status and host cell range remain unclear. In this study, we analyzed RV replication, infected cell types, and recovery of infectious virus in adenoids, palatine tonsils, and respiratory secretions from 293 children with tonsillar hypertrophy undergoing tonsillectomy. Samples were screened by real-time RT-PCR, and RV-positive samples were analyzed using immunohistochemistry (IHC), chromogenic in situ hybridization (CISH), flow cytometry, and RV isolation in cell culture. RV genotypes from species A, B, and C were identified in adenotonsillar samples. RV antigenome and structural proteins were detected in tonsillar epithelial surfaces, parenchyma, and in CD4 + T and B lymphocytes. Infectious RV was recovered from adenoids and respiratory secretions. In vitro infection of tonsillar mononuclear cells with RV-16 and RV-1A resulted in viral progeny production and secretion of distinct cytokine profiles. These findings demonstrate that RV infects tonsillar T and B lymphocytes, suggesting that tonsils can serve as sites of prolonged infection and sources of RV shedding. RV infection of immune cells may have potential impact on the local immune microenvironment.

Parkinson’s disease (PD), the second most common neurodegenerative disorder, is characterized by α-synuclein aggregation and loss of dopaminergic neurons, and current treatments are symptomatic. Multiple intricate mechanisms contribute to the pathogenesis, and the effectiveness of single-target approaches is therefore limited. Current approaches highlight therapeutic candidates capable of simultaneously modulating multiple pathways. Recent clinical and experimental studies of sodium-glucose cotransporter inhibitors (SGLT2is), approved for the treatment of type 2 diabetes mellitus, have indicated their pleiotropic and neuroprotective potential. SGLT2i dapagliflozin has several features, including low molecular weight, blood-brain barrier permeability, and tolerability. This study investigated the effects of dapagliflozin on pathways implicated in the pathogenesis of PD in a 6-hydroxydopamine-induced experimental PD model in female Sprague-Dawley rats using in silico, histopathological, immunohistochemical, and biochemical methods. Dapagliflozin was administered by oral gavage at four different doses (2.5 mg/kg, 5 mg/kg, 7.5 mg/kg, and 10 mg/kg) for 14 days. Motor deficits were evaluated by means of behavioral tests, and dapagliflozin was observed to alleviate motor dysfunction. Tyrosine hydroxylase expression increased in brain tissues, whereas A2AAR, TNF-α, and APAF-1 levels, as well as α-synuclein and caspase-3 expression, decreased. In molecular docking analyses, dapagliflozin showed notable binding affinity to PD-associated human target receptors. Our results suggest that dapagliflozin may exert potential neuroprotective effects via modulation of inflammatory, oxidative stress-related, and apoptosis-associated pathways and may represent a promising repurposing candidate for PD.

Pseudomonas aeruginosa is an opportunistic pathogen responsible for chronic infections in both human and veterinary medicine, with biofilm formation and multidrug resistance posing major clinical challenges. The efficacy of two bacteriophages, JG003 and PTLAW1, alone and in combination, was evaluated. In vitro biofilms grown on abiotic 96-well plates showed significant reduction after treatment with individual bacteriophages or their combination, as confirmed by confocal microscopy. To better simulate physiological conditions, efficacy was assessed using an epidermal equivalent model and an ex vivo canine skin model. In the ex vivo system, bacteriophage treatment reduced bacterial load by 4 logs, as confirmed by scanning electron microscopy and immunofluorescence imaging. In the epidermal equivalent model, bacteriophage therapy decreased bacterial counts and CXCL8 levels without inducing cytotoxicity or disrupting the skin barrier. Integration of in vitro and ex vivo systems bridges the gap between traditional biofilm assays and in vivo studies. The use of Franz-type diffusion cells provides a physiologically relevant platform for evaluating topical bacteriophage delivery and skin permeation. These findings establish a reproducible preclinical framework for biofilm-targeted therapies, demonstrating that bacteriophage combinations effectively reduce Pseudomonas aeruginosa biofilms and inflammation on skin, supporting their potential for wound treatment in both human and veterinary medicine.

Atherosclerosis is a chronic immunometabolic disease driven by lipid accumulation and immune cell infiltration. Macrophages and T cells play key roles throughout plaque development. Galectin-1 (Gal-1), a glycan-binding protein, modulates immune functions in these cells and has been reported to attenuate atherosclerosis, though its mechanisms remain incompletely understood. Here, we investigated the effects of Gal-1 on macrophages and T cells during plaque formation. Effects of Gal-1 on atherosclerosis, macrophages and T cells during lesion formation were studied in Apoe-/- mice treated with recombinant Gal-1. Complementary mouse peritoneal foam cell and in vitro macrophage and T cell culture experiments were performed to study T cell differentiation, macrophage function, polarization and energy metabolism. The impact of Gal-1 on human macrophages was further evaluated in endarterectomy specimens. Gal-1 treatment reduced lesion size and increased circulating IL-10 levels, inversely correlating with plaque burden. Unexpectedly, IL-10 neutralization also mitigated atherosclerosis, indicating that its action is at least partially IL-10-independent. In plaques, Gal-1 promoted anti-inflammatory macrophage phenotypes, mirrored by a quiescent metabolic and anti-inflammatory profile in foamy macrophages ex vivo. The use of the Gal-1E71Q variant revealed that these effects were only partly dependent on glycan binding. Beyond IL-10, Gal-1 reshaped cytokine profiles by increasing IL-17, IL-22, and IL-23, consistent with a macrophage-driven regulatory Th17 response, alongside higher frequencies of IL-10-producing and regulatory T cells. Gal-1 protects against atherosclerosis associated with reprogramming macrophages and tuning T cell immunity through glycan-dependent and -independent pathways.

Approximately 25% of human urothelial carcinoma (UC) cases progress to high-grade, muscle-invasive bladder cancer (MIBC), for which treatment response remains difficult to predict. To address the need for more predictive platforms, we developed an integrated in vitro-in silico system using canine UC derived organoids, which closely mirror human MIBC at the histological, molecular, and clinical levels. Organoids were irradiated at doses of 0, 5, 9, or 15 Gy and cisplatin was administered at concentrations of 0, 10, 25, 50, or 100 μM at 24 and 72 h post-plating, respectively. Cell viability was assessed one week later using a PrestoBlue metabolic activity assay. Combined effects of radiation and cisplatin were estimated using a two-dimensional Hill model, which disentangles synergism in magnitude of effect (efficacy) and potency, with directly interpretable parameters. Implementation within a Bayesian hierarchical model accommodated both between-subject and between-assay variation. The model showed inter-patient variability in response to both radiation and cisplatin, with varying potency for the radiation dose (posterior median ED50: 0.55-7.6 Gy) and cisplatin concentration (posterior median EC50: 40-174 μM), although in some cases the maximum effect fell outside the observed data range. Radiation had a generally greater contribution to the combined inhibitory effect than cisplatin. In selected cases, synergistic effects of chemoradiation were also identified, primarily in the efficacy dimension. These preliminary results establish a robust in vitro platform for assessing chemoradiation efficacy and potency, and provide essential data for the future development of personalized and optimized chemoradiation strategies in canine and human. UC.

Diabetes mellitus is a global chronic metabolic disorder characterized by elevated blood glucose levels, primarily due to impaired insulin activity or secretion. α-amylase, a key enzyme in carbohydrate digestion, is a validated molecular target for controlling postprandial hyperglycemia in type 2 diabetes. This study aimed to identify potential α-amylase inhibitors from phytochemicals derived from Bauhinia forficata, Citrus spp. and Echinops ritro using an in-silico approach. A total of 55 phytochemicals were virtually screened against human pancreatic α-amylase (PDB ID: 3BAJ) using molecular docking via Schrödinger Maestro (version 12.5). The top-ranked ligands were further assessed for pharmacokinetic and toxicity profiles using SwissADME, ProTox-II and StopTox platforms. Electronic reactivity was evaluated using Density Functional Theory (DFT) with Gaussian 09. Among the screened compounds, kaempferitrin (-10.3 kcal/mol), Rutin (-10.1 kcal/mol), Naringin (-9.7 kcal/mol) and Hyperoside (-9.6 kcal/mol) demonstrated strong binding affinities, favorable pharmacokinetic properties and compliance with drug-likeness criteria. DFT analysis supported their chemical reactivity and stability, indicating potential for biological activity. The results suggest that these phytochemicals could serve as promising lead molecules for the development of plant-based antidiabetic drugs targeting α-amylase. However, further experimental validation and mechanistic studies are recommended to confirm these findings.

Pre-clinical models are commonly used to determine human antibiotic dosage regimens using pharmacokinetic/pharmacodynamic (PKPD) indices. The murine thigh infection model (MTIM) is most commonly used for PKPD index determination, while the hollow fibre infection model (HFIM) may be a viable alternative. However, there is no standardized method for determining the PKPD index and R2 may not be the ideal metric to determine goodness of fit for nonlinear models. This study aimed to reanalyse PKPD indices published in MTIM and HFIM, using a standardized modelling approach. Systematic literature review was conducted to identify MTIM and HFIM dose fractionation studies. Searches covered databases including PubMed, MEDLINE, BIOSIS, SCOPUS and EMBASE. Data were extracted and modelled using eight variations of Emax model, with model selection based on the lowest Akaike information criterion (AIC) and parameter plausibility in terms of precision and interpretability. A total of 53 studies were included: 50 MTIM (of 1138) and 3 HFIM (of 316). Among the 53 studies, reporting issues included an infrequent use of AIC for model selection as applied in only one paper, and a lack of methodological transparency in 29 papers. Remodelling revealed some disagreement in optimal PKPD indices in six studies. This study suggests a standard method for PKPD index model selection and provides a database on PKPD index analysis. Building the Emax model from one to four estimated parameters and assessing them with AIC is recommended to avoid over fitting. Too few HFIM dose fractionation studies were found to allow comparison of PKPD index with MTIM.

1-Bromopropane, an alternative to ozone-depleting solvents, exhibits neurotoxicity in humans and rats. The aim of the present study was to identify the genes or signaling pathways involved in the neurotoxicity and hepatotoxicity of 1-bomopropane in two inbred strains of rats. F344 rats and WNA/NUM rats were exposed to 1-bromopropane or filtered air by inhalation for either a single 8-hour session, or 8 h daily for 4 weeks. Motor nerve conduction velocity and distal latency were measured in the tail. At the end of the experiment, the animals were decapitated, and the hippocampus, liver, and blood were collected. Exposure to 1-bromopropane for 4 weeks increased distal latency in the tail nerve significantly in F344 and marginally in WNA/NUM. It also increased total and direct bilirubin in both rat strains. Eight-hour exposure increased metallothionein 2A, metallothionein 1 and NAD(P)H quinone dehydrogenase 1 expression in the liver of both rat strains, whereas 4-week exposure upregulated glutathione S-transferase alpha 3 and CD36 molecule in the liver of both strains. KEGG analysis showed that 8-hr 1-bromopropane upregulated pathways of apoptosis, NOD-like receptor signaling and colorectal cancer, in both the hippocampus and liver, whereas 4-week exposure upregulated NOD-like receptor signaling pathway both in the hippocampus and liver of the two rat strains. Insulin signaling pathway was upregulated persistently in the hippocampus of the two rat strains. Our results suggest the involvement of immune system/inflammation-related pathway in the neuro- and hepato-toxicity of 1-bromopropane and the involvement of insulin signaling pathway in the neurotoxicity of 1-brromopropane.

BACKGROUND: The escalating challenge of acaricide resistance and the environmental concerns associated with synthetic tick control agents necessitate the development of sustainable, eco-friendly alternatives. The utilization of invasive plants for the synthesis of bioactive nanomaterials presents a promising strategy within integrated pest management. OBJECTIVE: This study aimed to evaluate the toxicity and behavioral effects of zinc oxide nanoparticles (ZnO-NPs) and essential oil (EO) derived from the invasive weed Ageratum conyzoides against the cattle tick, Rhipicephalus microplus. Methods: ZnO-NPs were synthesized using an aqueous leaf extract of A. conyzoides and characterized using UV-Vis spectroscopy, X-ray diffraction (XRD), and Fourier-Transform Infrared (FTIR) spectroscopy. While the analysis confirmed the crystalline wurtzite structure and phytochemical capping of the ZnO-NPs, their specific particle size and morphological characteristics were not determined in this study. The essential oil was extracted from the same plant via hydrodistillation. The contact toxicity of both the biosynthesized ZnO-NPs and the EO was tested. RESULTS: Characterization confirmed the successful synthesis of crystalline ZnO-NPs with a wurtzite structure and surface functionalization by plant phytochemicals. Bioassays revealed a potent, dose-dependent effect for both formulations. The ZnO-NPs induced rapid immobilization and mortality at the highest concentration (15%), while the EO caused complete paralysis, with both treatments showing significant intoxication and locomotor impairment (p&#x2009;<&#x2009;0.001). Statistical analysis confirmed a highly significant effect of both concentration and behavioral category for both ZnO-NPs and EO, underscoring their dose-dependent efficacy. CONCLUSION: This study successfully demonstrates that A. conyzoides is a valuable resource for generating effective acaricidal agents. The biosynthesized ZnO-NPs and the EO both show high potential as sustainable, green toxicants/control agents against ticks.

Xylazine, a veterinary sedative and alpha-2 adrenergic receptor agonist not approved for human use, has emerged as a significant adulterant in the illicit fentanyl supply across the United States. While its presence has been well documented on the East Coast, systematic reporting from California remains limited. This study characterizes the emergence, prevalence, and concentration trends of xylazine in forensic casework in San Francisco from 2022 January to 2024 December, and describes polysubstance patterns associated with its use. We retrospectively analyzed up to thirty-six (36) months of routine comprehensive toxicological testing for over 200 drugs/metabolites performed on all xylazine-positive accidental overdose deaths (AOD), driving under the influence of drugs (DUID), drug-facilitated sexual assault (DFSA), and public intoxication (PI) cases within the City and County of San Francisco, totaling 314 cases. Xylazine detections increased across all case types from 2023 to 2024 and rose steadily in AOD cases from 2022 through 2024. The majority of xylazine-positive cases were AOD. Mean and peak xylazine concentrations demonstrated year-to-year increases, with peak AOD blood and urine concentrations observed up to 31 and 2100 ng/mL, respectively. All xylazine-positive cases co-occurred with fentanyl, a fentanyl precursor or metabolite, or a fentanyl analog. Additionally, 71% of these cases involved five to eight additional drug classes. Xylazine has rapidly infiltrated the San Francisco illicit fentanyl supply and is frequently present in polysubstance use patterns. Rising prevalence and increasing concentrations indicate evolving market dynamics, with implications for overdose risk and forensic and public health surveillance.