Effects of acute THC challenge on behavior and neuroinflammation in HIV-1 Tg26 mice vary based on HIV status, chronic THC history, and sex.

Rapid antidepressant effects of Aurantii Fructus are mediated by hypoxanthine-caspase-4 axis in CUMS mice.

Malathion impairs sensory perception, learning, and memory, and increases oxidative stress in the western honeybee, Apis mellifera.

Bumblebees are efficient pollinators of fruits and vegetables in greenhouses and field crops. However, pesticide use in agricultural landscapes is causing a sharp decline in pollinating insect populations. The impact of pesticides on bumblebee health is a growing concern. Cyfluthrin, atrazine, and prothioconazole are 3 commonly used pesticides in agricultural production. Although the Food and Agriculture Organization of the United Nations has published the acute median lethal dose (LD50) data for these 3 pesticides on Apis mellifera honey bee, there is still a lack of LD50 data for non-Apis bees, such as Bombus terrestris (Linnaeus, 1758). Therefore, this study determined the oral median lethal dose (LD50) of 3 pesticides, cyfluthrin, atrazine, and prothioconazole, in European bumblebees (Bombus terrestris). The active ingredient of each pesticide was first dissolved in dimethyl sulfoxide and then diluted in a sucrose solution to prepare the pesticide-sucrose mixture for feeding. The oral LD50 values of cyfluthrin for worker bees were 4.27, 3.36, and 2.16 μg/bee at 24, 48, and 72 h, respectively. The 24-h LD50 for virgin queens was 13.49 μg/bee. For 24-h exposures in worker bees, the oral LD50 values of atrazine, prothioconazole, and their mixture were 355.3, 530.0, and 480.4 μg/bee, respectively. Pesticide-sucrose solution intake decreased as pesticide concentration increased. This study provides a preliminary evaluation of the toxicity of 3 pesticide types on bumblebees and offers insight for improving the conservation and sustainability of pollinators in agriculture. Additionally, the findings contribute to regulatory assessments by providing crucial data on pesticide effects on B. terrestris, supporting more comprehensive and effective pesticide regulations.

Ivabradine reduces seizure susceptibility in a genetic model of mixed epilepsies.

Kratom (Mitragyna speciosa) alkaloids influence on cardiopulmonary measures and high-fat diet-induced weight gain in mice.

Spent hemp biomass as a feed ingredient for beef steers: effects on performance, blood parameters, behavior, cannabinoid residues, and consumer exposure levels.

An Update on Animal Models of Alcohol-Associated Liver Disease.

ABSTRACTExtrapyramidal symptoms (EPS) are side effects observed after acute administration of D2 antagonists and nitric oxide synthase (NOS) inhibitors in rodents. To date, no study has examined NOS activity in parallel with c‐Fos immunoreactivity (c‐Fos‐IR) following multiple doses of these compounds. The aim of the present study was to evaluate whether catalepsy and motor balance deficits resulting from specific acute doses of haloperidol (Hal), metoclopramide (MCP), and L‐NOARG could correlate with changes in the number of c‐Fos‐IR and nNOS‐positive cells, as well as NADPH‐diaphorase activity in the striatum. Male Swiss mice received Hal (0.1–1 mg/kg, ip), MCP (1–45 mg/kg, ip), L‐NOARG (15–45 mg/kg, ip), or saline. An increased cataleptic effect was observed in all experimental groups. All doses of Hal and the higher doses of MCP resulted in deficits in the Rota‐rod test, whereas L‐NOARG did not affect Rota‐rod performance. Histochemical analysis revealed increased c‐Fos‐IR in the dorsal striatum following Hal, as well as in the dorsolateral striatum after low and intermediate clinically relevant doses of MCP. Both types of D2R antagonists led to an increase in NADPH‐diaphorase activity in the dorsal striatum. Similarly, the higher catalepsy‐inducing doses of L‐NOARG resulted in increased NADPH‐diaphorase activity in the dorsal striatum; however, these same doses also reduced c‐Fos‐IR in the dorsolateral striatum and nucleus accumbens (NAc). In conclusion, all drugs acutely induced catalepsy, with motor balance preserved after L‐NOARG treatment. Our findings suggest that EPS side effects may be attributed to NADPH‐diaphorase activity in the dorsal striatum.

Objective: The purpose of this study was to explore the effects of an acute dose of cannabidiol (CBD) on physical and mental health, as well as running performance in a group of runners. Methods: This study used a randomized, cross-over design where individuals were given CBD (CBD-T) or placebo (PLA-T) capsules on two separate occasions. During their first visit, the subjects consumed 300 mg of either placebo or CBD capsules and were then instructed to sit quietly for 2 h. Then, participants filled out a State Trait Anxiety Inventory (STAI) and completed measures of resting systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), blood lactate (BL), and heart rate variability (HRV). Next, participants completed a 2-mile treadmill run as fast as possible. During each run, HR, rating of perceived exertion (RPE), and BL were measured during and after the run. Participants completed a gastrointestinal (GI) symptom questionnaire immediately after the 2-mile time trial. Results: Participants (N = 12; 4 males, 8 females) averaged 25.5 years ± 3.34 years of age. Mean CBD-T reported increased feelings of calm (21% p = 0.04) and relaxed (22%, p = 0.02) when compared to PLA-T. There were no differences in the severity of GI symptoms, SBP, DBP, or HRV between the treatments. The CBD-T experienced an 8% reduction in average RPE at mile 1 of the run compared with PLA-T (p = 0.05). There was no significant difference in run performance time. Conclusions: An acute dose of CBD (300 mg) taken 2 h before a 2-mile run may potentially benefit runners in shorter distance competitions by increasing calm and relaxed feelings and reducing perceived effort at the halfway point without impairing performance or increasing gastrointestinal upset.

Fate and cumulative risk assessment of typical pesticides in celery cultivated in summer cool open fields.

Background/Objectives: Dietary inorganic nitrate (NO3−), primarily sourced from vegetables such as beetroot, has been shown to enhance nitric oxide (NO) bioavailability, with emerging evidence suggesting its potential to modulate autonomic function. However, the effects of NO3− supplementation on cardiac autonomic recovery post-exercise in hypertensive postmenopausal women remain poorly understood. Using data from a previously conducted randomised controlled trial, this study investigated the effects of acute (800 mg) and seven-day (400 mg/day) beetroot juice NO3− supplementation on ultra-short-term post-exercise cardiac parasympathetic recovery in hypertensive older women. Methods: In a triple-blind, placebo-controlled crossover design, fourteen postmenopausal women (59 ± 4 y) with hypertension completed two intervention arms (NO3− and placebo). Ultra-short-term heart rate variability (HRV) indices (SDNN, RMSSD, HF) were assessed across 5 min post-exercise recovery using 60 s windows. Plasma NO2− and NO3− concentrations were measured via chemiluminescence. Results: Both acute and seven-day NO3− supplementation significantly increased plasma NO2− and NO3− concentrations compared to placebo (p < 0.001). Cardiac vagal recovery, assessed via SDNN and RMSSD, was significantly enhanced in both conditions, with greater and more sustained improvements observed after the seven-day protocol. HF power was significantly higher, but only after seven-day supplementation (p = 0.009). Conclusions: Inorganic NO3− supplementation enhances post-exercise cardiac parasympathetic reactivation in hypertensive postmenopausal women. Notably, the seven-day intake (400 mg/day) protocol elicited superior autonomic benefits compared to an acute high dose. These findings highlight the potential of NO3− as a non-pharmacological strategy for improving cardiovascular autonomic recovery in high-risk populations.

ObjectivesExposure of the developing fetus to high doses of ionizing radiation during prenatal development can result in growth restriction of the fetus, or a reduction in offspring growth. The developmental stage of the offspring at the time of irradiation is of interest, in order to characterize any potential periods of sensitivity for radiation-induced growth restriction effects. The goal of the present study was the development of a mouse model of radiation-induced growth restriction, following X-ray irradiation during late gestation.MethodsPregnant BALB/cAnNCrl mice were irradiated with different irradiation conditions from gestational day (GD) 14-17. Treatments included an acute dose of 1.82 Gy X-ray irradiation on GD 14, 15 or 16. The effects of dose fractionation were also studied with one group receiving 0.455 Gy x 4 daily fractions from GD 14-17 (cumulative dose of 1.82 Gy). Another group also received a pre-treatment with 61 mGy X-ray irradiation on GD 14, 24 h prior to the 1.82 Gy on GD 15, to test for the possibility of a radiation-induced adaptive response.ResultsEvidence for growth restriction was observed in all irradiation groups, with the greatest degree of growth restriction observed in the 1.82 Gy on GD 14 group. Evidence for growth restriction was based on a reduced gestational weight gain by pregnant dams and significant decrease in fetal weight and length measurements. Evidence for an adaptive response was not observed in the present study, as the combination group had similar outcomes to the group that only received the 1.82 Gy challenge irradiation dose.ConclusionThe establishment of a mouse model of radiation-induced growth restriction during late gestation will facilitate the ability for future work into determining the precise cellular and physiological effects on offspring, and the development of future countermeasures to protect against such adverse effects.

Childhood trauma is associated with positive subjective responses to acute opioids in the laboratory. Yet, its impact on behavioural economic demand for opioids remains unclear. Because demand can predict future use and misuse, we investigated whether individuals with childhood trauma also display greater demand for opioids in the laboratory. This secondary analysis used data from a double-blind, randomised, controlled, counterbalanced trial. Across two sessions, individuals with (n = 26) and without (n = 21) childhood trauma received a high (0.15mg/kg) and low (0.01mg/kg) dose of intramuscular morphine 120min before a hypothetical purchase task. Participants also regularly reported their subjective desire for the study drug. Area under the consumption and expenditure curves, and specific demand indices (Omax, Pmax, breakpoint, intensity, elasticity), were analysed with non-parametric mixed models. Consumption and expenditure for low dose morphine was lower in the childhood trauma group when compared to high dose morphine in this group, and low dose morphine in the control group (ps ≤ 0.03). Consistent results were obtained for specific demand indices Omax, Pmax, and breakpoint, but not intensity or elasticity. Positive correlations between subjective desire and consumption and expenditure were only observed in the childhood trauma group (Tau-c = 0.24-0.34, ps ≤ 0.03). Under laboratory conditions, desires to use opioids among individuals with childhood traumas may not manifest in strong intentions to acquire these drugs. Diverging results from psychometric measures of subjective and economic opioid value highlight the need for future research to explore contextual and resilience factors to understand how problematic opioid use emerges after childhood traumas.

This review synthesizes current evidence on therapeutic strategies for Parkinson's disease (PD)-related overactive bladder (OAB), encompassing PD-targeted treatments, pharmacologic interventions, and advanced therapies such as neuromodulation and intravesical botulinum toxin. We address the complexity of managing lower urinary tract symptoms (LUTS) in patients with PD due to progressive neurodegeneration affecting micturition control and cognitive vulnerabilities in this population. A thorough review of available literature shows that chronic levodopa improves bladder capacity and reduces urgency, though acute dosing may worsen symptoms in advanced stages. Subthalamic nucleus-deep brain stimulation enhances bladder function and symptom scores, possibly by modulating basal ganglia-thalamocortical circuits. Anticholinergics are effective but pose cognitive risks, warranting careful use guided by anticholinergic burden assessments. In contrast, beta-3 agonists such as mirabegron offer a safer cognitive profile with emerging efficacy data. Finally, intravesical botulinum toxin and neuromodulation present promising third-line options, though data in PD remain limited, and larger trials are still needed to confirm their role. Optimal management of LUTS in PD requires individualized, stage-specific, multidisciplinary strategies balancing efficacy and cognitive safety. Further high-quality, disease-specific studies are essential to develop tailored treatment algorithms and improve quality of life in this growing patient population.

In vitro and in vivo toxicological evaluation of 6'-Sialyllactose sodium salt produced by a novel method.

Fipronil is an insecticide with low residual activity and high efficacy at low concentrations. Due to its widespread use and long half-life, fipronil can persist during wastewater treatment and is found even in surface waters. When released into the environment, it can accumulate over time and can lead to concentrations in soil and plant tissues that are harmful to both target and non-target organisms. As the reuse of treated wastewater and sewage sludge presents challenges and opportunities for farmers, this study investigates the effects of irrigation with environmentally relevant doses of fipronil on zucchini plants and their main insect pest, Aphis gossypii. Traces of fipronil were found in the zucchini leaves, but not in the flowers, after 35-days of cumulative exposure. A decrease in nymph-to-adult survival and a dose-dependent reduction in the fecundity of A. gossypii feeding on contaminated host plants was observed. Also, aphids feeding on contaminated host plants exhibited the same mortality rate as the control group when exposed to an acute dose of fipronil. However, when natural pyrethrins were used, there was a significant increase in resistance to this insecticide. Our results demonstrate the potential for fipronil to accumulate in plant tissues and highlight the risk of changes in insecticide susceptibility in insect pests. This suggests a need for a holistic approach to the complex dynamics of wastewater reuse in agriculture.

Ionizing radiation continues to be weaponized not only through the development of nuclear weapons, but also on a smaller scale through the development of radiological dispersal devices, or dirty bombs. Exposure to acute doses of ionizing radiation often leads to the development of acute radiation syndrome (ARS), for which treatment options are currently limited. Current treatment options include only post-exposure prophylaxes that are intended to restore bone marrow function and stimulate platelet production. To date, no pre-exposure prophylaxes are available to treat ARS, although many pharmaceuticals are currently under evaluation. Amifostine, for example, has been investigated as a radioprotector, but was found unsuitable due to its hypotensive effects, severe upper and lower gastrointestinal disturbances, and reduced efficacy at the doses required for effective radioprotection. RadioDefender, an amifostine-based drug, shows promise as a radioprotector due to its ability to shield bone marrow from the deleterious effects of ionizing radiation, offering protection at lower doses than those required for amifostine without the toxic effects. Two separate toxicity studies were performed: the first study investigated the effects of various doses of RadioDefender on blood and lymphoid tissue in unirradiated mice to establish the no-observed-adverse-effects-level (NOAEL), while the second study investigated the effects of various doses of RadioDefender on tissue and metabolomic profiles in irradiated mice (9.2 Gy total-body γ-irradiation). RadioDefender treatment significantly improved survival and provided substantial protection in the steroid hormone biosynthesis and arachidonic acid metabolism pathways, key pathways involved in inflammation and immune response that have been proven to be highly sensitive to ionizing radiation.

Quantum dots (QDs), especially metal oxide QDs, possess properties such as size-tunable band gaps and a high surface-to-volume ratio that are exceptionally advantageous in biomedical applications. In this study, we synthesized zinc oxide quantum dots (ZnO-QDs) and polyethylene glycol (PEG) functionalized ZnO-QDs (PFQD) and characterized them using transmission electron microscopy, UV-vis absorption spectroscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction. An in vivo acute toxicity analysis of ZnO-QD and PFQD was conducted over 96h. The LD50 values for both the ZnO-QD and PFQD were 144.082 and 225.246µg/g b.w., respectively. Following the acute toxicity assessment, a sub-acute toxicity test was conducted to assess the effects on bioaccumulation, as well as hematological, histological, and enzymatic parameters, oxidative responses, and genotoxicity in fish. This was achieved by administering 1/50 of the LD50 values of the acute dose to fish, alongside a control group, over 14days. PFQD relative to the ZnO-QD nanoparticles showed significantly lower bioaccumulation of Zn levels (ppm/g) in both liver and head kidney tissues (p < 0.05). ZnO-QD exposure reduced erythrocyte count, hemoglobin levels, and hematocrit, with increased leukocyte and platelet counts, while PFQD caused fewer hematological alterations. According to serum biochemical indicators, ZnO-QD exposure caused hepatic and renal damage, inflammation, histopathological changes, and an apoptotic assay (as determined from DNA laddering and DAPI Annexin V-FITC staining), contrasting with PFQD. In the liver and kidney, macrophages (Kupffer and mesangial cells) showed that ZnO-QDs enhanced lipid peroxidation and significantly lowered antioxidant defenses. In contrast, PFQD decreased LPO and increased antioxidant enzyme activity. In conclusion, this study suggests that PFQD exhibits superior radical scavenging capabilities, positioning it as a potential antioxidant and a better biocompatible agent.

Mushroom production and economic value on a global scale are significantly increasing. On the other hand, food safety has raised concerns; however, limited research exists on the presence of plant growth regulator (PGR) residues in edible mushrooms. Herein, this study appears to be the first to comprehensively investigate PGR residual characteristics and assess their associated dietary exposure risks to consumers. A total of 105 edible mushroom samples of seven different varieties were analyzed, and the overall detection rate was 81%. The residual level of PGRs ranged from below the limit of detection to 6.308 mg/kg. Among varieties, 100% of A. aegerita, T. fuciformis Berk, and H. erinaceus samples contained at least one PGR residue. Dietary exposure risks were assessed using both deterministic and probabilistic approaches. Calculated values of both %ADI (acceptable daily intake) and %ARfD (acute reference dose)were below 100 and do not indicate a potential health concern with respect to edible mushroom consumption. However, several PGRs had a relatively high %ADI or %ARfD value, suggesting that the Maximum Residual Limits (MRLs) and associated regulatory norms should be immediately established. This work not only provides valuable information for edible mushroom consumers but also an important reference for the risk management decision.