An unprecedented global effort is currently underway to move away from animal studies and toward more human-relevant methods. While this shift is gaining momentum in biomedical research and preclinical safety assessment, how does it extend to the toxicological and regulatory evaluation of food contaminants? This review examines the current state of foodborne contaminant assessment, specifically mycotoxins, emphasizing both emerging efforts and persistent barriers to implementing an animal-free testing paradigm. Several initiatives from regulatory bodies signal a strong commitment to change. However, major challenges remain. Additionally, animal use in the European Union continues to be widespread in procedures related to food and feed safety, as well as in hazard assessment studies addressing exposure to mycotoxins. These considerations emphasize an urgent call to action to promote human-relevant approaches and advance safety assessment practices in the context of 21 st century technologies. • Global efforts are moving toxicology assessment away from animal studies. • Regulatory integration of NAMs in food safety remains limited. • Mycotoxin risk assessment represents an example of the slow adoption of NAMs. • Momentum from biomedical research should now drive innovation in food safety.

Engineered tissue constructs are typically evaluated by extensive animal studies to assess their in vivo efficacy. Histological analysis is the widely used approach. However, this technique is time-consuming and highly dependent on experienced pathologists. Moreover, it provides limited insight into how tissue continuously changes at the same tissue site over time. In this study, we propose a deep learning (DL)-based model, Bone Tissue Prediction Generative Adversarial Network (BTP-GAN), which integrates synthetic histological image generation with a biological tissue growth model to simulate bone tissue development over time. Despite a small training dataset, the generated histological images are biologically meaningful and realistic, owing to three algorithmic modules: the Analysis module, Growth module, and Generation module. Moreover, Ordinary Differential Equations (ODE)-Transformer model can learn the temporal patterns and structural characteristics of real tissue images, enabling the generation of histological images according to various specific generative conditions. The BTP-GAN successfully demonstrates the continuous histological change at the same bone tissue site, relying only on a single input histological image. This in-silico animal study may change the perception of the necessity of extensive animal studies in tissue engineering and provide a practical framework for the future advancement of in-silico tissue engineering.

This systematic review explores the application of Raman spectroscopy (RS) in traumatic brain injury (TBI) research, emphasizing the need for innovative and efficient diagnostic tools. The development of such techniques aims to alleviate healthcare costs while providing timely assessment of injury severity. A systematic literature search for the use of RS in TBI was conducted in PubMed, Scopus, and Web of Science from inception to July 28, 2025, following PRISMA guidelines. We included only original English-language studies (animals and humans) in free full-text format. Risk of bias was assessed using specific tools for both animal and human models. Findings were classified according to the cohorts, and spectroscopic technique alongside their particularities. The initial search found 261 articles, with 26 studies meeting the inclusion criteria. Among them: 15 were animal studies and 11 translational/human-relevant studies. Among animal studies, 3 focused on in-situ monitoring and TBI classification, 2 on blast-induced models, 5 on blood biomarker analysis, 2 on retinal-based point-of-care diagnostics, and 3 on Raman microscopy. The translational research studies aimed to identify and validate TBI biomarkers for developing future diagnostic strategies in human patients. RS distinguished injured from control tissue through spectral changes reflecting protein and lipid alterations and differentiated lesion areas by revealing astrogliosis-related reorganization. Instantaneous in-situ RS devices achieved >92% accuracy in severity classification and detected biomarker-related molecular changes. Point-of-care RS platforms using lateral flow strips enabled rapid detection of specific TBI biomarkers (GFAP, NAA, NSE, S100B, UCH-L1), showing performance comparable to ELISA while offering faster, simpler, and cost-efficient testing.

Homelessness is associated with an increased risk of stroke, likely secondary to uncontrolled vascular risk factors and poor access to preventive care and chronic disease management. Its specific impact on acute stroke care and outcomes remains poorly understood. In this study, we conducted a systematic review and meta-analysis to summarize the available evidence. We searched PubMed, EMBASE, PsycINFO, Scopus, and Web of Science from 2000 to 2024 without language or geographical restrictions. Original observational studies of adults with acute stroke experiencing homelessness were included. Studies in animals and children, and studies without clear characterization of housing status and stroke outcomes were excluded. We compared post-stroke mortality, use of cerebrovascular diagnostics and therapeutics (including intravenous thrombolysis [IVT], mechanical thrombectomy, and vessel imaging), discharge destinations, and length of hospital stay between patients experiencing homelessness (PEH) and housed patients. We conducted a meta-analysis by pooling relative risk effect size. Titles and abstracts of 1,598 articles were screened by two independent reviewers, and 80 studies were selected for full-text review. Seven studies comprising 620,327 (86.5% male, 54.5 average age) PEH and 3,035,234 (52.7% male, 57.4 average age) housed patients were included in the systematic review. Studies included in the meta-analysis were conducted in the United States. All seven studies were rated as moderate to high quality. Pooled analysis did not reveal differences in in-hospital mortality between PEH and housed patients (risk ratio [RR]; 1.10 95% confidence interval [CI] 0.82-1.48). PEH with ischemic stroke were receiving IVT less frequently compared to housed individuals (RR 0.86, 95% CI 0.77-0.97). Two studies reported on discharge destinations, both indicating that PEH were more likely to be discharged to self-care or leave against medical advice. Patients experiencing homelessness with stroke were less likely to receive IVT and more often discharged without support. Further research is needed to identify long-term stroke outcomes and address disparities of post-stroke care to improve outcomes in PEH with stroke. Prospero (Registration No. CRD42024582119).

Alzheimer's disease (AD) is an increasing health and social problem worldwide with prevalent cholinergic cell involvement. To reveal the details of the exact mechanisms, further preclinical studies in animals are needed. Our aim was to create a mouse model that represents the progression of AD with easy cholinergic manipulation. The 3xTg-AD and ChAT-Cre strains were crossbred. After serial genotyping, a colony, homozygote for all four genes (PSEN1, APPSwe, tauP301L and Cre; 3xAD-ChAT-Cre) was established. The presence of amyloid-β (Aβ) plaques and phosphor-Tau (pTau) aggregates was confirmed by immunohistochemistry. To test the functionality of the Cre enzyme, a stimulating DREADD virus (AAV8-hSyn-DIO-hM3Dq-mCherry) was injected unilaterally into the nucleus basalis magnocellularis, and clozapine-N-oxide-induced c-Fos activation was compared between the two hemispheres. Behavioral characterization was performed using the Y-maze, social discrimination (SDT), single pellet reaching (SPR), fox odor (FOT), and splash tests (ST). Food, water consumption and body weight change were investigated. Immunostaining and RNAscope confirmed the expression of Cre in ChAT-positive cells and the progressive appearance of pathological hallmarks (Aβ and pTau). The c-Fos activity was significantly increased in the virus-injected hemisphere. Compared with control mice, 3xAD-ChAT-Cre mice showed decreased locomotion (Y-maze, SDT, FOT), increased anxiety (FOT, ST) and weaker fine motor skills (SPR). In conclusion, newly created animals have a functional Cre recombinase enzyme in cholinergic cells. Additionally, the animals presented the pathophysiological hallmarks of AD in specific brain areas and maintained the typical behavioral alterations previously reported in 3xTg-AD mice. Thus, this strain seems to be appropriate for further studies.

Purpose To evaluate the prognostic utility of cardiac MRI parameters, particularly native T1 and extracellular volume fraction (ECV), for predicting early mortality in a preclinical model of anthracycline-induced cardiotoxicity. Materials and Methods Thirty-one Sprague-Dawley rats received weekly intravenous doxorubicin injections (2 mg/kg) for up to 12 weeks and were followed up until natural death. Cardiac MRI, including parametric mapping sequences, was performed. Myocardial histology was evaluated after death. Cox proportional hazards regression with time-dependent covariates was used to assess the association between MRI variables and early death. Results Of the 31 rats, 17 (55%) died before 12 weeks (early death group), and 14 survived to study completion. In the early death group, native T1 and ECV increased between weeks 4 and 6 (from 1210.51 msec ± 53.75 to 1368.09 msec ± 60.11 and from 17.52% ± 2.05 to 21.63% ± 2.22, respectively; both P < .001). At week 6, both parameters were higher in the early death group than in the survival group (1368.09 msec ± 60.11 vs 1243.10 msec ± 55.71, P = .003; 21.63% ± 2.22 vs 18.47% ± 2.13, P = .045). In univariable analyses, native T1 (hazard ratio, 1.01; 95% CI: 1.00, 1.01; P < .001) and ECV (hazard ratio, 1.17; 95% CI: 1.04, 1.32; P = .01) were statistically significantly associated with early death. A model combining native T1 and ECV achieved a C-index of 0.76 (95% CI: 0.64, 0.92). Conclusion Native T1 and ECV were good predictors of early mortality in rats with anthracycline-induced cardiotoxicity. Keywords: Animal Studies, MR-Imaging, Cardiac, Myocardium, Experimental Investigations Supplemental material is available for this article. © RSNA, 2026.

Formaldehyde use in the anatomy laboratory and the pregnant or breastfeeding student dissector navigating the challenges of toxicological uncertainty and institutional policy.

Hemodynamic and pathological Effects of aortic occlusion during Resuscitation: An ex vivo circulatory platform and in vivo animal study.

Ensuring the safety of fragrances is a priority for both consumers and industry. The Research Institute for Fragrance Materials (RIFM) conducts risk assessments using a transparent framework. In the past, evaluating systemic toxicity relied on animal studies mandated by regulatory requirements; however, RIFM has not conducted new animal toxicity studies for over a decade. Of note, the doses used in these studies far exceed everyday exposure to fragrance ingredients. While toxicologists recognize the gap between test doses and real exposure, it may not be obvious to an average fragrance user. To illustrate this, the No-Observed-Adverse-Effect Levels (NOAEL) and Human Equivalent Doses (HED) of benzaldehyde and p-cymene were determined. As benzaldehyde and p-cymene occur in fragrances and foods, we used intake in food and fragrance use as a comparator. For fragrance exposure, the Creme RIFM Aggregate Exposure model was utilized. Results showed that adverse effect levels require ingesting about 166,000 almonds (for benzaldehyde) or 307,407 raspberries (for p-cymene) daily, or applying 276,660 sprays of benzaldehyde and 37,220 sprays of p-cymene daily. The selected exposure scenarios emphasize that data from animal studies must be viewed in the context of human exposure, highlighting advances in exposure science for realistic risk assessment.

Characterization of the pathogenicity of newly emerged NADC30-Like PRRSV strains causing severe brain infections via twice inter-lineage recombination.

The influence of baseline sleep on responses to new stressors: A systematic review.

In vitro, ex vivo, and in vivo evaluation of ophthalmic ointments containing dexamethasone and tobramycin.

Propolis is a bioactive bee product that may influence adipokines involved in metabolic and inflammatory disorders; however, findings on leptin, adiponectin, and resistin are inconsistent across models and human studies. Current study aimed to systematically synthesize preclinical and clinical evidence on the effects of propolis and propolis-derived compounds on leptin, adiponectin, and resistin, and to summarize proposed mechanistic pathways. The study protocol was registered in PROSPERO (CRD42024593198). We searched PubMed, Web of Science, Scopus, and Google Scholar to find related articles published between 1900 and 2025. We screened reference lists, and used alert services after the primary search. We included in vitro, animal, and human studies that were published in English language and evaluated propolis/propolis-derived compounds versus a comparator and reporting leptin, adiponectin, and resistin outcomes. Risk of bias was assessed using the CRIS guideline (in vitro), SYRCLE tool (animal), and Cochrane risk-of-bias tool (clinical trials). Findings were synthesized narratively due to heterogeneity. Twenty-six studies were included (9 in vitro, 11 animals, 6 human). In vitro studies generally reported decreased leptin and resistin expression and increased adiponectin expression following propolis-derived phenolics; one study reported increased leptin mRNA with a Brazilian propolis extract. In animal studies, leptin decreased in 5/8 studies and adiponectin increased in 5/9 studies, while remaining studies reported no change or opposite directions. Human trials showed mixed results: leptin decreased in 1/2 trials and adiponectin increased in 2/5 trials, whereas other trials reported no significant change. Substantial heterogeneity in propolis type/origin, formulation, dose, duration, and participant health status limited comparability. Preclinical evidence suggests that propolis and selected constituents can modulate adipokines (often lowering leptin/resistin and increasing adiponectin), but clinical evidence is limited and inconsistent. Well-designed, adequately powered trials using standardized propolis preparations are required to clarify efficacy and translational relevance. The online version contains supplementary material available at 10.1007/s40200-026-01855-1.

Junctophilin-2 abundance is unaltered in human heart failure samples with disrupted T-tubules and contractility.

Effects of Cytochrome P450 enzymes and drug-drug interaction on donafenib metabolism: in vivo, in vitro and in silico.

The optimal tidal volume (VT) during Cardio-Pulmonary Resuscitation (CPR) remains unknown. Capnogram could permit to detect ventilation induced harmful effect. The objectives of the present study were to describe the impact of different VT on hemodynamics during CPR; and to evaluate whether capnogram analysis can assess the influence of ventilation on circulation. Eighteen pigs had five minutes of untreated ventricular fibrillation followed by CPR with automated continuous chest compressions and ventilation settings randomly combining VT 6, 10 or 14ml/kg. Capnograms were recorded to determine thoracic distension patterns. After return of spontaneous circulation (ROSC), all surviving animals were ventilated 2h and lungs were withdrawn for histological analysis. VT was associated with differences in the hemodynamic parameters studied. VT at 6 or 14ml/kg graphically showed poorer cerebral and coronary perfusion pressures and mean arterial pressure than a VT at 10ml/kg. The capnogram could distinguish three levels of thoracic distension. Thoracic distension was associated with differences in the hemodynamic parameters studied. Animals with either low or high distension showed poorer cerebral and coronary perfusion pressures and mean arterial pressure than those with moderate distension. ROSC was obtained in 13 (72%) animals. Histology showed that both low and high VT was associated with a trend towards higher lung damage. In this animal study, a U-shaped relationship observed with VT suggests that both small and large VT may impair circulation. Capnogram analysis could contribute to identify ventilation settings associated with hemodynamic compromise.

Persistent use of black stone for snakebite envenoming in tropical and subtropical Asia and Africa: a literature review.

Meniscal extracellular matrix remodelling caused by injuries and degeneration

Anxiety in male psoriasis mouse model is mediated by the interaction between γδ T cell-derived IL-17A and microglia.

Anxiety-like behaviors are highly prevalent and frequently co-occur with metabolic conditions such as type 2 diabetes and obesity, suggesting the potential for shared biological mechanisms. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for glycemic control and weight management, emerging evidence indicates that they may also influence neuroinflammation, neuroplasticity, and affective regulation. However, findings across preclinical and clinical studies remain fragmented, and no systematic synthesis has directly evaluated their effects on anxiety-like behaviors. This review addresses this gap by examining whether GLP-1 RA administration reduces anxiety-like behaviors or clinically coded anxiety outcomes. Following PRISMA guidelines, preclinical and clinical studies were systematically identified, screened using PICOS-defined criteria, and evaluated with validated quality assessment tools. Across animal studies, GLP-1 RAs consistently reduced anxiety-like behaviors and improved neurobiological markers related to stress resilience, while clinical cohorts demonstrated mixed but suggestive evidence of reduced anxiety incidence and lower suicidal ideation risk. These findings highlight the potential for GLP-1 RAs to modulate both metabolic and psychiatric pathways, underscoring the need for randomized controlled trials to clarify causal effects and inform their role in metabolic psychiatry.