Search Results (455)

Background/Objectives: The receptor for advanced glycation end products (RAGEs) has been implicated in obesity and metabolic dysfunction. However, its precise role in diet-induced obesity remains unclear. Methods: In this study, we investigated the metabolic consequences of RAGE knockout (RAGE KO) in mice subjected to a Western diet (WD). Results: Our findings demonstrate that RAGE KO mice remained significantly leaner than their wild-type (WT) counterparts when fed a WD, exhibiting reduced body weight gain and smaller adipocyte size. Indirect calorimetry revealed that RAGE KO mice had increased oxygen consumption and locomotor activity compared to WT mice, indicating enhanced energy expenditure. Mitochondrial respiration assays indicated significantly greater oxygen consumption in RAGE KO animals. Additionally, systemic inflammation markers, such as TNF-α, were significantly lower in RAGE KO mice when fed a WD, indicating a reduction in diet-induced inflammatory responses. Conclusions: These findings suggest that RAGE plays a key role in metabolic homeostasis, and its deletion confers resistance to obesity and metabolic disruption induced by a Western diet. Targeting RAGE may provide a novel therapeutic approach for combating obesity and related metabolic disorders. Full article

Breast cancer (BC) is the most common type of cancer in women worldwide. Hexokinase II (HKII) overexpression is associated with the proliferation and survival of tumor cells, as it inhibits apoptosis. Incomptine A (IA) is cytotoxic to breast cancer cells, likely due to a decrease in the expression of HKII. This study evaluated the antitumor activity of IA in an in vivo mouse model of BC. A model was generated from 4T1 cells and grouped tumor-bearing animals according to treatment: in IA or doxorubicin (DOXO), or untreated (UT). Comparing the body weight and tumor size between groups, tumors were analyzed using histopathological, Western blot, flow cytometry, and mitochondrial activity assays. Tumors IA-treated showed a reduction in size, weight, and number of tumor cells; the expression of HKII and Bcl-2 decreased, while that of Caspase-3 increased. IA treatment increased apoptosis and reduced mitochondrial activity in tumor cells. This data showed that IA has an impact on tumor cells by reducing tumor volume and size, increasing cell apoptosis, and decreasing mitochondrial activity, all of which could be attributed to reduced HKII expression. Therefore, IA may be a promising compound that requires further studies to elucidate its mechanism of action and analyze its possible future use in BC. Full article

In this study, we analyzed data from 2992 cows to comprehensively evaluate the adult weight (WEI), a key growth and body-size indicator, in West China cattle, aiming to estimate the related phenotypic and genetic parameters. The analysis focused on four weight traits while considering non-genetic factors such as parity, season, year, and birth weight. Data were processed and corrected using a MIXED procedure and a multi-trait animal model. Results showed that these non-genetic factors significantly affected the weight traits (p < 0.05), which had high heritability (0.25–0.39) (p < 0.01). WEI is crucial for improving the genetic traits of cattle in western China and provides innovative approaches for optimizing herd management, enhancing the efficiency of genetic selection, and boosting beef cattle productivity. Full article

Introduction: Given the impact of aneurysmal subarachnoid hemorrhage (aSAH) on patients’ health, preclinical research is substantial to understand its pathophysiology and improve treatment strategies, which necessitates reliable and comprehensive animal models. Traditionally, aSAH models utilize iliac or subclavian access for angiography, requiring invasive procedures that are associated with significant risks and animal burden. This pilot study explores a less invasive method of digital subtraction angiography (DSA) by using the auricular artery (AA) as an alternative access point. Our aim was to demonstrate the feasibility of this refined technique, with the intention of reducing procedural risks, providing shorter operation times with enhanced neurological recovery, and simplifying the process for both researchers and animals. Materials and Methods: In this study, six female New Zealand white rabbits (3.2–4.1 kg body weight) underwent experimental induction of aSAH via a subclavian-cisternal shunt. The initial steps of this procedure followed traditional techniques, consisting of subclavian access through microsurgical preparation, followed by DSA to analyze retrograde filling of the basilar artery (BA). To evaluate the alternative method, on day 3 after induction of aSAH, DSA was performed via the AA instead of the traditional subclavian or femoral access. A catheter was placed in the AA to allow retrograde filling of the BA. This approach aimed to simplify the procedure while maintaining comparable imaging quality. Results: All rabbits survived until the study endpoint. Postoperatively, two rabbits showed signs of hemisyndrome, which significantly improved by the time of follow-up. No additional morbidities were observed. Upon euthanasia and necropsy, all animals showed clear subarachnoid bleeding patterns. DSA via the AA produced strong contrasting of the BA comparable to the traditional method. Conclusions: This technical note presents an initial evaluation of AA access as a feasible and potentially advantageous method for DSA in a rabbit model of blood shunt subarachnoid hemorrhage. The method shows promise in reducing invasiveness and procedural complexity, but further studies are required to fully establish its efficacy and safety. Future research should focus on expanding the sample size, refining the anatomical understanding of the AA, and continuing to align with ethical considerations regarding animal welfare. Full article

Accurate estimation of metabolizable energy requirements (MER) is essential for appropriate dietary planning in dogs. However, standardized recommendations may not reflect the variability observed in clinical practice, particularly regarding individual factors such as neutering status, body condition, and age. This study aimed to retrospectively assess the MER factor in dogs treated at a Brazilian veterinary hospital, considering variables including sex, neuter status, body condition score (BCS), muscle mass score (MMS), body size, and life stage, and to compare the findings with those typically reported in the scientific literature. A total of 438 medical records from 2013 to 2025 were reviewed for this study. Data on demographic and clinical variables were collected, and MER factors were calculated based on energy intake and body weight. Statistical analyses were conducted to evaluate the interactions between variables, particularly BCS and neutering status. The study population included 253 males (57.8%) and 185 females (42.2%), with 80.6% of them being neutered. The MER values varied widely across the subgroups. Neutered dogs had consistently lower energy factors than intact dogs (p < 0.0001), and energy requirements decreased progressively with increasing BCS, regardless of neutering status (p < 0.05). A significant interaction between BCS and neutering status was observed (p = 0.0089), although BCS alone was not a significant predictor (p = 0.9670). No substantial differences were observed based on sex, body size, or life stage. MER values observed in clinical practice differ from standard recommendations and are influenced by the interaction between neutering status and body condition. These findings reinforce the need for individualized nutritional assessments in companion animal medicine and call for further studies to refine clinical energy estimation models. Full article

Brachycephalic head shape in dogs has been associated with behavioural traits that may enhance their appeal as companion animals, contributing to their popularity. However, it remains unclear whether these behavioural differences are directly linked to head shape or are mediated by factors such as body size, demographics, and dog-keeping practices. Drawing on two large-scale owner surveys (N = 5613) and cephalic index estimates for 90 breeds, we investigated the relationship between head shape and eight behavioural variables (four personality traits and four behavioural problems), while controlling for 20 demographic and dog-keeping characteristics, as well as body size. Our results show that behavioural differences among head shapes are only partly attributable to head shape itself; some are explained by confounding variables. Specifically, brachycephalic dogs appeared predisposed to positive behaviours (e.g., calmness, fewer behavioural problems), but these traits were often obscured by their small body size and low training experience. These findings highlight the complex interplay between morphology, behaviour, and environment, and emphasize the role of training and management in supporting the behavioural well-being of popular brachycephalic breeds. This has important implications for owners, breeders, and welfare professionals aiming to align aesthetic preferences with behavioural and welfare outcomes. Full article

Thyroid hormones (thyroxine, T₄, and triiodothyronine, T₃) are indispensable for sustaining vertebrate life, and their deficiency gives rise to a wide range of symptoms characteristic of hypothyroidism, affecting 5–10% of the world’s population. The precursor for thyroid hormone synthesis is thyroglobulin (Tg), a large iodoglycoprotein consisting of upstream regions I-II-III (responsible for synthesis of most T₄) and the C-terminal CholinEsterase-Like (ChEL) domain (responsible for synthesis of most T₃, which can also be generated extrathyroidally by T₄ deiodination). Using CRISPR/Cas9-mediated mutagenesis, we engineered a knock-in of secretory ChEL into the endogenous TG locus. Secretory ChEL acquires Golgi-type glycans and is properly delivered to the thyroid follicle lumen, where T₃ is first formed. Homozygous knock-in mice are capable of thyroidal T₃ synthesis but largely incompetent for T₄ synthesis such that T₄-to-T₃ conversion contributes little. Instead, T₃ production is regulated thyroidally by thyrotropin (TSH). Compared to cog/cog mice with conventional hypothyroidism (low serum T₄ and T₃), the body size of ChEL-knock-in mice is larger; although, these animals with profound T₄ deficiency did exhibit a marked elevation of serum TSH and a large goiter, despite normal circulating T₃ levels. ChEL knock-in mice exhibited a normal expression of hepatic markers of thyroid hormone action but impaired locomotor activities and increased anxiety-like behavior, highlighting tissue-specific differences in T₃ versus T₄ action, reflecting key considerations in patients receiving thyroid hormone replacement therapy. Full article

In modern society, obesity and its associated complications have emerged as serious public health concerns, primarily stemming from sedentary lifestyles and carbohydrate-rich diets. Due to the severe side effects often associated with pharmacological anti-obesity agents, emerging global efforts focus on preventive strategies, e.g., dietary modifications and weight gain-suppressing functional foods. In this context, plant-derived metabolites are extensively investigated for their beneficial anti-obesity effects. In this study, we evaluated how Rosa rugosa Thunb. flower bud extract affects fat metabolism in 3T3-L1 preadipocyte cells. The extract significantly inhibited adipocyte differentiation and intracellular triglyceride accumulation in 3T3-L1 cells, enhanced lipolysis, suppressed lipogenesis, and promoted energy metabolism in differentiated adipocytes. In vivo, it reduced body and organ weights and fat mass in high-fat diet-induced obese rats, along with marked adipocyte size and hepatic lipid accumulation reductions. In the epididymal adipose tissue, the extract similarly enhanced lipolytic activity, suppressed lipogenic enzyme expression, and stimulated energy expenditure. Taken together, our results demonstrate the potential of R. rugosa Thunb. flower bud extract in reducing fat accumulation through lipid metabolism modulation both in cellular and animal models. Further studies are warranted to identify the active constituents and evaluate the safety and efficacy of the extract in clinical applications. Full article

Accurate body condition score (BCS) monitoring in dairy cows is essential for optimizing health, productivity, and welfare. Traditional manual scoring methods are labor-intensive and subjective, driving interest in automated imaging-based systems. This study evaluated the effectiveness of 2D imaging and deep learning for BCS classification using three camera perspectives—front, back, and top-down—to identify the most reliable viewpoint. The research involved 56 Norwegian Red milking cows at the Center for Livestock Experiments (SHF) of Norges Miljo-og Biovitenskaplige Universitet (NMBU) in Norway. Images were classified into BCS categories of 2.5, 3.0, and 3.5 using a YOLOv8 model. The back view achieved the highest classification precision (mAP@0.5 = 0.439), confirming that key morphological features for BCS assessment are best captured from this angle. Challenges included misclassification due to overlapping features, especially in Class 2.5 and background data. The study recommends improvements in algorithmic feature extraction, dataset expansion, and multi-view integration to enhance accuracy. Integration with precision farming tools enables continuous monitoring and early detection of health issues. This research highlights the potential of 2D imaging as a cost-effective alternative to 3D systems, particularly for small and medium-sized farms, supporting more effective herd management and improved animal welfare. Full article

Sexual dimorphism is prevalent among animals, influencing both functional morphological traits and behavioral performances. In this study, we investigated the sexual differences in the morphological parameters of Kaloula borealis (Anura, Microhylidae) during the breeding season using 48 specimens. Our results reveal that among the 16 external morphological traits, females had significantly larger snout-vent length and eye diameter than males. The former presumably contributes to enhancing fertility, while the latter is associated with larger body size. Males exhibited significantly greater head width and thigh width than females, which may be related to accessing a wider range of food sources and enhancing their locomotor ability, respectively. Among the 32 appendicular muscles, 10 displayed significant sexual dimorphism in dry mass, suggesting divergent reproductive strategies between the sexes. Among the eight internal organs analyzed, males possessed significantly heavier hearts and lungs than females, which is likely an adaptation to higher metabolic demands and calling behavior. Collectively, our findings demonstrate that sex-specific differences in external morphology, muscle mass, and internal organ mass reflect distinct ecological and reproductive adaptations between males and females and contribute to the phenotypic diversities in Anura. Full article

Developing a new drug costs approximately one to three billion dollars and takes around ten years; however, this process has only a ten percent success rate. To address this issue, new technologies that combine artificial intelligence (AI) and quantum computing can be leveraged in the pharmaceutical industry. The RSA cryptographic algorithm, developed by Rivest, Shamir, and Adleman in 1977, is one of the most widely used public-key encryption schemes in modern digital security. Its security foundation lies in the computational difficulty of factoring the product of two large prime numbers, a problem considered intractable for classical computers when the key size is sufficiently large (e.g., 2048 bits or more). A future application of using a detailed structural model of a protein is that digital drug design can be used to predict potential drug candidates, thereby reducing or eliminating the need for time-consuming laboratory and animal testing. Knowing the molecular structure of a possible candidate drug can provide insights into how drugs interact with targets at an atomic level, at significantly lower expenditures, and with maximum effectiveness. AI and quantum computers can rapidly screen out potential new drug candidates, determine the toxicity level of a known drug, and eliminate drugs with high toxicity at the beginning of the drug development phase, thereby avoiding expensive laboratory and animal testing. The Food and Drug Administration (FDA) and other regulatory bodies are increasingly supporting the use of in silico to in vitro/in vivo validation methods and assessments of drug safety and efficacy. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) is the most common oral cancer, progressing from hyperplasia to dysplasia, carcinoma in situ (CIS), and finally invasive squamous cell carcinoma (ISCC). Developing an animal model that mimics both early and advanced OSCC stages has been challenging. The 4-Nitroquinoline 1-oxide (4NQO) model is considered one of the most suitable, as it represents all stages of OSCC. Nevertheless, thoroughly understanding the properties of the 4NQO model is essential for preclinical testing of novel therapeutics. Methods: We aimed to characterize the 4NQO rat model using two application methods—drinking water and topical application—over eight months. Monthly sacrifices allowed histopathological analysis and ex vivo magnetic resonance imaging (MRI) to track tumor progression. Results: CIS was observed at three months in the drinking water group, evolving into ISCC by six months, while topical application induced CIS at eight months without ISCC formation. The tongue was divided into three regions and histological properties, lesion size, and invasion depth were analyzed. In the drinking water group, particularly in the body of the tongue, we saw earlier CIS development, larger lesions, and deeper invasion. Additionally, assessment of proliferative properties showed an increased cell division in dysplastic lesions that reduced upon invasion. MRI was able to show macroscopic tumoral lesions, in concordance with histology. Conclusions: Overall, the drinking water method closely mimics human OSCC, validating the 4NQO model for translational OSCC research. Full article

Understanding the motion behaviors of animals is crucial for unraveling the mechanisms underlying ethology across various domains, such as movement patterns, food detection, and defense strategies. In this study, we devised a simplified method enabling the movement of small animals to be tracked conveniently using high-resolution smartphone videos and freely available tracking software. Employing a laboratory video setup, we traced the swimming trajectory of the small copepod zooplankton Eodiaptomus japonicus, which has a body size of approximately 1 mm. From the tracked position data, we analyzed key motion parameters, including swimming distance, speed, and jump frequency. The results of our video analysis showed that adult female E. japonicus exhibited an average swimming speed of 9.8 mm s⁻¹, displaying a predominant cruising pattern with speeds of around 5.0 mm s⁻¹, punctuated by sporadic jumps, showcasing maximum instantaneous speeds reaching a remarkable 190.1 mm s⁻¹. Our successful tracking of the high-speed swimming copepod not only sheds light on its locomotion dynamics but also underscores the potential to refine this method to study the motion trajectories of diverse animal species. Full article

Critical-sized bone defects (CSBDs) are injuries that exceed the body’s natural capacity for repair and require external intervention. These defects are particularly challenging in the mandible, often resulting from trauma, tumor resection, or implant-related complications. Effective treatment involves scaffold designs that support vascularization, bone formation, and sufficient mechanical strength. This systematic review aims to assess whether ceramic-based scaffold properties, including porosity, pore size, and macroscopic characteristics, improve vascularization, bone formation, and the mechanical properties in the treatment of CSBDs in large animal models. A search of databases (PubMed, Embase, and Web of Science) identified 11 in vivo studies involving CSBDs (>2 cm), ceramic scaffolds, and histological analysis. Findings indicate that scaffolds with porosity exceeding 50% yield optimal outcomes by striking a balance between cell infiltration and mechanical stability. Pore sizes ranging from 300 μm to 700 μm are ideal for vascularization and bone ingrowth. Three-dimensional (3D) printing shows promise in creating scaffolds with precise and reproducible features. However, the studies varied significantly in their methodologies and outcomes, with no consensus on the optimal scaffold properties for mandibular CSBDs. Scaffold porosity and pore size play key roles in promoting vascularization and bone regeneration. Various animal models reinforce this finding, suggesting that scaffold architecture is crucial for biological integration and functional outcomes. This review highlights the importance of standardized research protocols and clear design criteria in enhancing the success of bone regeneration. Future research should investigate emerging biomaterials and new scaffold technologies to overcome current limitations in clinical applications. Full article

The high production of plastic, along with its biostability and poorly managed recycling, has led to its widespread presence in the environment. Pollution from microplastics (particles smaller than 5 mm) and nanoplastics (particles smaller than 1 μm) poses a serious environmental problem, with long-term negative impacts on human and animal health. The goal of this systematic review is to identify the toxicokinetics of microplastics and nanoplastics after they are ingested by mammals. A total of 1057 articles were identified in the PubMed database, Web of Science, and Google Scholar through a manual search. After removing duplicates, 560 articles remained. Upon reviewing the titles and abstracts, 500 articles were excluded. Out of the remaining 60 articles, 43 were excluded, and 17 were included in the study. The current clinical evidence indicates that plastics can enter the body in the form of microplastics and nanoplastics. The digestive system is a significant pathway for absorption, and the resulting changes are influenced by factors such as the type of plastic, the duration of exposure, the particle size, and the individual’s clinical condition. Once absorbed, plastic particles can enter the body and cause significant changes in intestinal barrier function, hepatic metabolic changes, oxidative stress, and nephrotoxicity. Full article