Search Results (6,427)

The pathogenesis of primary osteoarthritis (OA) is complex and multifactorial. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a transcription factor that regulates hundreds of genes involved with cytoprotection. The role of Nrf2 in OA remains undefined. We utilized the Hartley guinea pig model of primary OA to investigate the role of a purported Nrf2 activator, PB125, in delaying the onset of knee OA. We hypothesized that three months of daily PB125 supplementation would modify structural, molecular, and in vivo functional outcomes characteristic of disease. Fifty-six 2-month-old animals (equal sexes) were treated orally with PB125 or vehicle control for 3 months; animals were sacrificed at 5 months, which represents mild OA and early disease. Outcome measures included knee histopathology, mRNA expression, immunohistochemistry, and in vivo mobility. Notably, PB125 treatment had differing effects in males and females. Female PB125-treated animals had significantly decreased distal femur OA scores, accompanied by differential gene and protein expression patterns in articular cartilage for markers related to redox homeostasis; decreases in one compulsory mobility metric were also seen. In contrast, males demonstrated a statistical difference in voluntary mobility patterns. In summary, PB125 may modify the molecular mechanisms involved in the initiation of early OA in a potential sex-dependent fashion. Full article

Bovines are suitable hosts and can be affected by fly infestations. Flies pose a significant threat to cattle livestock in Latin America (LA), causing substantial economic repercussions to animal production (reduced productivity, veterinary expenses, and decreased animal welfare) and damage to human health. The most important flies affecting cattle in Argentina, Brazil, Colombia, Mexico, and Uruguay are Haematobia irritans, Dermatobia hominis, and Cochliomyia hominivorax. Due to production losses and the consequent economic costs associated with these flies, control measures must be implemented, primarily relying on insecticidal products. However, decision-making for preventing and treating animals with insecticides varies due to differences in environmental conditions across countries and regions, production systems, animal populations, infestation levels, animal welfare, and the prevalence of myiasis, among other factors. Although insecticides remain the most effective option for fly control in cattle, resistant populations have developed, rendering them less effective. To overcome fly resistance to insecticides, non-chemical (mechanical, environmental, biological, and genetic) methods are being integrated into alternative control and eradication strategies. The use of integrated livestock fly control contributes to safeguarding animal, public, and environmental health. This review is designed to support individuals and institutions, both civil and governmental, addressing the ongoing challenge posed by flies affecting livestock. Full article

Pain associated with routine husbandry procedures in sheep can persist for several days or even weeks, yet current analgesic options, such as the non-steroidal anti-inflammatory drug (NSAID) meloxicam, typically provide only 24–36 h of analgesia. This mismatch between pain duration and analgesic coverage represents a fundamental limitation of current pain-management strategies in sheep. Sustained-release (SR) formulations are emerging as a promising approach to deliver longer-lasting pain relief from a single dose, reducing the need for repeated handling, and improving both animal welfare and farm efficiency. Emerging evidence highlights both the promise and limitations of different strategies to extend therapeutic coverage beyond 72 h. While preliminary results are encouraging, challenges remain in achieving consistent pharmacokinetic profiles and optimal peak concentrations. Advancing SR meloxicam formulations could support widespread uptake of welfare-focused innovations in the sheep industry. Although not yet widely available, sustained-release meloxicam represent a promising step towards making routine husbandry procedures more humane and efficient. Full article

Oncosomes, a distinct subclass of extracellular vesicles released predominantly by tumor cells, have attracted increasing interest as potential carriers for targeted drug delivery in cancer research. Characterized by their large size (1–10 µm) and complex molecular cargo, including oncogenic proteins, nucleic acids, and lipids, oncosomes provide a biologically relevant platform for investigating tumor-associated communication and cargo transport. Preclinical studies suggest that oncosomes may enable tumor-associated delivery of therapeutic agents; however, evidence to date remains largely proof-of-concept and derived from in vitro and animal models. This review summarizes current knowledge on oncosome biogenesis and molecular composition; discusses their roles in cancer progression and metastasis; and critically evaluates existing methodologies for oncosome isolation, characterization, and cargo loading, including incubation, electroporation, sonication, freeze–thaw cycling, and transfection. Potential advantages such as cargo capacity and biological compatibility are discussed alongside key challenges, including vesicle heterogeneity, limited loading efficiency, large-scale manufacturing constraints, safety considerations, and regulatory uncertainty. Future perspectives focus on addressing these technical and translational barriers to support the systematic evaluation of engineered oncosomes as an experimental platform for personalized and precision-oriented cancer research. Full article

Background: Cardiotoxicity is a major limitation of chemotherapy and radiotherapy for thoracic and systemic cancers, contributing significantly to morbidity and mortality among survivors. Early prediction and prevention are critical to balance oncologic efficacy with cardiovascular safety. Artificial intelligence (AI) offers powerful tools to improve risk stratification, enable earlier detection of subclinical injury, and guide treatment planning in cardio-oncology. Methods: We performed a comprehensive review of the literature on AI applications for cancer therapy-related cardiotoxicity. Evidence was identified from PubMed, Scopus, and Web of Science, focusing on electrocardiography, biomarkers, proteomics, extracellular vesicles, genomics, advanced imaging (echocardiography, cardiac magnetic resonance, computed tomography, nuclear imaging), and radiotherapy dose modeling (dosiomics). Translational insights from animal models and in vitro systems were also included. Methodological quality was appraised with reference to TRIPOD-AI, PROBAST-AI, and CLAIM standards. Results: AI applications span multiple domains. Machine learning models integrating biomarkers, exosomes, and extracellular vesicles show promise for noninvasive early detection. Deep learning enables automated analysis of echocardiographic strain and cardiac MRI mapping, while radiomics and dosiomics approaches combine imaging with cardiac substructure dose maps to predict and prevent late radiation-induced injury. Preclinical studies demonstrate AI-driven advances in small-animal imaging, histopathology quantification, and multi-omics data integration, supporting the discovery of translational biomarkers. Despite encouraging performance, most models remain limited by small cohorts, methodological heterogeneity, and scarce external validation. Conclusions: AI has the potential to transform cardio-oncology by shifting from reactive detection to proactive prevention of cardiotoxicity. Future research should prioritize multimodal integration, harmonized multicenter datasets, prospective validation, and guideline-based clinical trials. As emerging data are incorporated, the field is expanding rapidly—dynamic, complex, and evolving. Full article

Feed stress is a very critical factor impacting livestock health and productivity. One of the major contributors to quantitative feed deficiency is the continued adherence to conventional diets and feeding practices, which renders livestock populations vulnerable to environment-induced scarcity events as well as shortages arising from supply-chain bottlenecks. These challenges occur in the face of the ever-expanding demand from a continuously growing livestock population. In a world increasingly experiencing qualitative and quantitative resource constraints due to rising demand and increasing pollutant concentrations in the environment, conventional dietary compositions require timely modification and supplementation with alternative feed ingredients. These may include the hitherto unutilized by-products of agricultural production, which are often discarded as agricultural waste, in order to mitigate the stress induced by feed availability shortfalls. Cauliflower leaf meal is one such by-product whose suitability as a feed supplement was evaluated in the present study, with results that can be reliably described as promising. The present study assessed the impact of dried cauliflower leaf meal (CLM) on growth performance, nutrient utilization, rumen fermentation, and methane emission in goats. Fifteen non-descript male goats, aged 6–8 months, were randomly allocated into three groups of five animals each and housed separately in identical pens within the same shed for the duration of the experiment. Three dietary treatments were administered: T0 (control; concentrate, hybrid Napier, and wheat straw); T20 (20% replacement of wheat bran with CLM in the concentrate, along with hybrid Napier and wheat straw); and T30 (30% replacement of wheat bran with CLM in the concentrate, along with hybrid Napier and wheat straw). The results indicated that the goats in all groups achieved a similar body-weight gain with a comparable dry-matter intake (DMI). The feed conversion ratio (FCR), nutrient digestibility, and mineral balance were also comparable across treatments. However, the methane emission rate was significantly lower (p < 0.05) in the T30 group compared with the other groups. CLM supplementation did not cause deviations in rumen pH, NH₃-N concentration, volatile fatty acid production, or bacterial and protozoal populations. The hematological parameters remained unaffected by the increased dietary inclusion of CLM, while both cell-mediated and humoral immune responses showed an improvement in the CLM-fed groups. Notable reductions in methane emission were observed in goats fed diets containing 20–30% dried CLM, highlighting the positive environmental implications of such a dietary inclusion. Full article

Objectives. Pancreatic cancer remains one of the most lethal malignancies, and the lack of effective therapies highlights the need for novel treatment strategies. In this study, we evaluated the antitumor potential of the attenuated Streptococcus pyogenes strain GURSA1—engineered to knockout the M protein completely—in a murine model of orthotopically transplanted pancreatic ductal adenocarcinoma. Methods. Female C57Bl/6 mice received intratumoral injections of GURSA1 at doses of 5 × 10⁵ or 1 × 10⁶ CFU per animal. Animal survival, body weight, tumor engraftment, metastasis intensity, tumor mass and volume, and hematological, biochemical, histological, and microbiological parameters were assessed. Results. Intratumoral administration of GURSA1 produced dose-dependent antitumor effects on tumor growth and metastatic burden, but did not result in a statistically significant survival benefit. The strain reduced tumor engraftment, the overall metastasis score, and the incidence of hemorrhagic ascites, while also decreasing tumor mass and volume, with the strongest effects observed at a dose of 1 × 10⁶ CFU. Treatment increased platelet counts and reduced urea and ALT levels toward values observed in intact mice, without affecting anemia, neutrophilia, or changes in AST, alkaline phosphatase, glucose, and total protein levels. Conclusions. These findings demonstrate that GURSA1 attenuates partial reduction in primary tumor burden in vivo and support further investigation of this strain as a potential oncolytic agent. Full article

Helicobacter pylori is a major causative agent of chronic gastritis, gastric and duodenal ulcers, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. Transmission to humans may occur through the consumption of contaminated food. This study investigated the prevalence of H. pylori in fresh raw meat from different animal sources and assessed the efficiency of selective media for its recovery in Dhamar Governorate, Yemen. A total of 380 meat samples, including beef (n = 125), sheep (n = 135), and goat (n = 120), were collected from slaughterhouses (n = 127), retail markets (n = 124), and butcher shops (n = 129). Three selective media: Modified Campy-blood Agar (MCA), Belo Horizonte Agar (BHA), and Egg Yolk Emulsion (EYE) medium were evaluated for comparative recovery from each meat source. Overall, H. pylori was detected in 47 samples (12.4%), with a relatively high prevalence in beef (15.2%), followed by goat (12.5%) and sheep (9.6%). By source, butcher shop samples comparatively showed the highest prevalence (15.5%), especially in beef (19.1%), goat (14.3%), and sheep (13.3%), as compared to the slaughterhouses (11.8%) and retail markets (9.7%). Differences among meat types and sources were not statistically significant (p = 0.394 and p = 0.362). Overall, selective media comparison revealed that MCA showed a relatively high recovery rate (6.6%), followed by EYE (3.4%) and BHA (2.4%). A seasonal trend was observed, with peak prevalence in April (20%). These findings suggest that raw meat may represent a potential source of exposure to H. pylori, although its role in transmission to humans remains to be fully clarified. Regular monitoring, improved hygiene practices, and stricter control of environmental contamination are recommended to reduce associated public health risks. Full article

Automatic recognition of endangered animal behavior is crucial for biodiversity conservation and improving animal welfare, yet traditional manual observation remains inefficient and invasive. This work contributes directly to sustainable wildlife management by enabling non-invasive, scalable, and efficient monitoring, which supports long-term ecological balance and aligns with several United Nations Sustainable Development Goals (SDGs), particularly SDG 15 (Life on Land) and SDG 12 (Responsible Consumption and Production). The current deep learning approaches often struggle with the scarcity of behavioral data and complex environments, leading to poor model generalization. To address these challenges, this study focuses on endangered animal behavior monitoring and proposes a multimodal learning framework termed ABCLIP. This model leverages multimodal contrastive learning between video-and-text pairs, utilizing natural language supervision to enhance representation ability. The framework integrates pre-training, prompt learning, and fine-tuning to optimize performance specifically for small-scale animal behavior datasets, with a focus on the specific social and ecological behaviors of giant pandas. The experimental results demonstrate that ABCLIP achieves remarkable accuracy and robustness in recognizing endangered animal behaviors, attaining Top-1 and Top-5 accuracy of 82.50% and 99.25%, respectively, on the LoTE-Animal dataset, which outperforms strong baseline methods such as SlowFast (78.54%/97.55%). Furthermore, in zero-shot recognition scenarios for unseen behaviors, ABCLIP achieves an accuracy of 58.00%. This study highlights the potential of multimodal contrastive learning in wildlife monitoring and provides efficient technical support for precise protection measures and scientific management of endangered species. Full article

Paternal deprivation has behavioral, neurochemical, and neuroendocrine consequences in adulthood. Socially monogamous prairie voles (Microtus ochrogaster) raised only by the mother (monoparental care, MP) showed low levels of alloparental behavior and delayed pair bonding formation in adulthood compared to those raised by both parents (biparental care, BP). However, the effects of paternal deprivation on adult neurogenesis and the epigenetic mechanisms involved remain to be elucidated. Here, we focused on the impact of MP rearing on neural stem cells (NSCs) proliferation under basal conditions and in response to cohabitation with the sexual partner during pair bonding formation. At basal conditions, we found a significant decrease in the number of new proliferative NSCs (BrdU⁺/SOX2⁺) in male and female MP voles compared to BP animals in the subventricular (SVZ) and subgranular zone (SGZ). After 24 h of cohabitation, in MP males, there was an increase in the number of newborn cells in the SVZ but not in the SGZ. However, this increased proliferation was lower than in BP males. In females, we did not observe significant differences compared to controls. Finally, we evaluated the enrichment of H3K4me3 (activation) and H3K27me3 (silencing) epigenetic marks in the new cells, finding differences between rearing systems and sexes. Full article

Background: Caveolin-1 (Cav-1) is a protein found in various forms and locations within cells and tissues throughout the body. Studying its structure and function provides valuable insights into key cellular processes such as growth, death, and cell signaling. This review synthesizes evidence from human studies and animal models to elucidate the complex role of Caveolin-1 (Cav-1) in regulating nitric oxide (NO) synthesis within the vasculature and perivascular adipose tissue (PVAT) during atherosclerosis. Cav-1 is a master regulator of endothelial NO synthase (eNOS), a relationship well-defined in rodent endothelial cells and cell lines. In humans, loss-of-function CAV1 mutations are linked to pulmonary arterial hypertension, suggesting a protective vascular role. Paradoxically, Cav-1 is upregulated in atherosclerotic plaques. Whether this represents a pathological process reducing NO bioavailability or a compensatory response remains unclear. Furthermore, the direct translation of the Cav-1/eNOS axis to PVAT—a metabolically active tissue expressing Cav-1—is not fully established outside of preclinical models. PVAT influences vascular tone and inflammation, potentially contributing to the paradoxical, stage-specific roles of Cav-1 in disease. Resolving these questions requires integrating human observational data with mechanistic insights from animal models to evaluate Cav-1 as a therapeutic target in vascular disease. Full article

Despite the increasing adoption of desktop virtual reality (VR) in higher education, the specific instructional efficacy of 3D interactive prompts remains inadequately understood. This study examines how such prompts—specifically dynamic spatial annotations and 3D animated demonstrations—influence learning outcomes within a desktop virtual learning environment (DVLE). Employing a quasi-experimental design integrated with eye-tracking and multimodal learning analytics, university students were assigned to either an experimental group (DVLE with 3D prompts) or a control group (basic DVLE) while completing physics tasks. Data collection encompassed eye-tracking metrics (fixation heatmaps, pupil diameter and dwell time), post-test performance (assessing knowledge comprehension and spatial problem-solving), and cognitive load ratings. Results indicated that the experimental group achieved significantly superior learning outcomes, particularly in spatial understanding and dynamic reasoning, alongside optimized visual attention patterns—characterized by shorter initial fixation latency and prolonged fixation on key 3D elements—and reduced cognitive load. Eye-tracking metrics were positively correlated with post-test scores, confirming that 3D prompts enhance learning by improving spatial attention guidance. These findings demonstrate that embedding 3D interactive prompts in DVLEs effectively directs visual attention, alleviates cognitive burden, and improves learning efficiency, offering valuable implications for the design of immersive educational settings. Full article

Amyotrophic Lateral Sclerosis (ALS) is a devastating neuromuscular disorder characterized by the progressive loss of motor neurons and skeletal muscle, ultimately leading to respiratory failure and death, typically within 3–5 years following diagnosis. While the death of motor neurons is the pathological hallmark, ALS is increasingly recognized as a systemic disorder involving non-motor systems. Gastrointestinal dysfunction has been widely observed in both ALS patients and animal models. However, because gut abnormalities and neuromuscular degeneration are intertwined during ALS disease progression, it remains unclear whether these gut abnormalities are merely a consequence of neuromuscular degeneration or whether they play a crucial role in initiating it. In this study, we investigated whether an ALS-associated mutation expressed exclusively in the gut can directly affect neuromuscular function. We generated a novel transgenic mouse model, Gut-hG93A, which overexpresses the human ALS mutation hSOD1^G93A specifically in the epithelial cells of the intestine at a level comparable to the endogenous mouse SOD1. We found that the specific overexpression of hSOD1^G93A in gut epithelial cells did not cause abnormalities in the structure of the tight junctions or in gut permeability. Furthermore, there were no significant differences between Gut-hG93A and control mice regarding lifespan, body weight, or neuromuscular activities, including grip strength, daily travel distance and in vivo muscle contractility. These findings suggest that the ALS-associated hSOD1^G93A mutation, when expressed solely in the gut epithelium, is not sufficient to initiate neuromuscular degeneration of systemic ALS-like pathology. Full article

Background: Ketamine and magnesium sulfate are commonly used perioperatively to prevent shivering, a frequent and clinically relevant complication of spinal and general anesthesia. Although their hypothermic effects are well documented, the neurotransmitter mechanisms underlying these effects remain insufficiently understood. This study examines whether serotonergic, adrenergic (α₂), and GABAergic (GABA_A) systems contribute to hypothermia induced by ketamine and a ketamine–magnesium sulfate combination. Methods: Body temperature was measured in Wistar rats after administration of ketamine (10 mg/kg) or the ketamine (5 mg/kg)–magnesium sulfate (5 mg/kg) combination. To assess neurotransmitter involvement, animals received yohimbine (α₂ antagonist), methysergide (non-selective 5-HT antagonist), or bicuculline (GABA_A antagonist) prior to ketamine or the drug combination. Data were analyzed using two-way repeated measures ANOVA followed by Tukey’s post hoc test. Results: Yohimbine at 0.5 and 1 mg/kg significantly potentiated ketamine-induced hypothermia, while only 3 mg/kg enhanced the effect of the ketamine–magnesium sulfate combination. Methysergide had a bidirectional influence: 1 mg/kg methysergide deepened ketamine-induced hypothermia, whereas 0.5 mg/kg methysergide attenuated the hypothermic effect of the ketamine–magnesium sulfate combination. Bicuculline (1–2 mg/kg) did not alter the hypothermic responses to ketamine or the combination. Conclusions: These findings indicate that ketamine- and ketamine–magnesium sulfate-induced hypothermia is primarily modulated by serotonergic and adrenergic mechanisms, whereas GABA_A receptor-dependent pathways do not appear to play a major role under the experimental conditions used. These results provide new mechanistic insights into NMDA antagonist–related thermoregulation and may help inform anesthetic strategies for shivering prevention and maintenance of perioperative thermal stability. Full article

As the critical component of the gastrointestinal tract, which lives in trillions of gut microorganisms, in a healthy state, the host interacts with the gut microbiota and is symbiotic. The species Limosilactobacillus reuteri, Ligilactobacillus salivarius, and Lactobacillus johnsonii are indigenous gut commensal bacteria that are mainly found in the digestive tracts. These three bacteria possess a variety of characteristics that reflect their ability to adapt to the gastrointestinal environment. Herein, we summarize the current progress of research on the probiotic properties of these strains in terms of their ability to protect against harmful pathogens, maintain intestinal health, and improve disease outcomes. These bacteria can impact the intestinal barrier function and enhance intestinal immunity through various mechanisms, such as upregulating the tight-junction protein expression and mucin secretion of intestinal epithelial cells, adjusting and balancing the gut microbiota, and blocking pro-inflammatory cytokine production. They have been shown to ameliorate intestinal inflammation in animal models and provide protective effects against various healthy issues in humans, including diarrhea, constipation, colorectal cancer, obesity, and liver diseases. However, the detailed mechanisms of certain strains remain unclear. Full article