Search Results (5,221)

Simulation of a human neurological disease on an animal model has the advantage of allowing control and manipulation of most of the regulating factors and producing real biological replicas while, beyond several common traits, every human is dynamic and unique. Moreover, one can explore novel therapeutic strategies on animals before asking permission to apply them to humans. Nevertheless, experimental outcomes depend on species, strain, sex, age, hormonal status, diet, exposure to hypoxia, toxins, radiation, external stimuli, stress, and housing conditions. Further complications stem from tissue hetero-cellularity, technological constraints, computational complexity and difficulties integrating the experimental results into a coherent biological picture. Moreover, most diseases are multi-factorial and associated with altered structure and/or expression of several genes. A major problem with genetically engineered animals is that together with the targeted gene(s), numerous other genes are mutated and/or regulated, owing to their interlinkage in functional pathways. This experience-based methodological commentary presents the challenges, relevance and limitations of the mouse, rat and rabbit models we used to decipher the transcriptomic alterations associated with several neurological disorders. Links to publicly accessible databases presenting experimental protocols and expression profiles are provided for readers interested in reanalyzing our data and comparing them with others’ results. Full article

Obesity is a multifactorial disorder with increasing global prevalence, highlighting the importance of identifying early-life factors that may influence long-term metabolic outcomes. While metformin is widely used to improve metabolic dysfunction in adulthood, whether neonatal exposure to this drug modifies adult responses to subsequent dietary challenges remains poorly understood. This exploratory study evaluated whether intraperitoneal metformin administration during the neonatal period alters adult metabolic responses to hyperlipidic diet (HL) exposure in Wistar rats. Following weaning and sex determination, male offspring (n = 80) were included in the study and distributed among four experimental groups, i.e., saline–normolipidic (SAL-NL), saline–high-fat (SAL-HL), metformin–normolipidic (MET-NL), and metformin–high-fat (MET-HL), with 20 animals per group. From postnatal days 1 to 12, animals received daily intraperitoneal saline or metformin (100 mg/kg/day). From days 60 to 90, animals were fed normolipidic or hyperlipidic diets. Body mass, food intake, glucose tolerance (GTT), and insulin tolerance (ITT) were assessed. Neonatal metformin exposure was associated with reduced body mass gain in MET-HL animals compared to SAL-HL, while food intake differed according to dietary condition. Metformin-treated animals also exhibited improved insulin sensitivity, reflected by higher kITT values, while no significant differences were observed in glucose tolerance. These preliminary findings suggest that neonatal metformin administration may influence adult metabolic responses to dietary challenge. Further studies are required to elucidate the mechanisms and long-term implications of this early-life intervention. Full article

Fruit and vegetable waste (FVW) from large-scale retail is an abundant, relatively homogeneous feedstock for black soldier fly (Hermetia illucens) larvae, an alternative to composting. This study assessed, by life cycle assessment (LCA), the environmental performance of a pilot plant producing 15-day-old larvae as animal protein and tested whether the additive conditioning of the FVW changes that performance. Three substrates were compared (FVW with 20% bakery waste, 20% bran, and 2% sawdust, respectively) using climate change (GWP100a, IPCC 2007), economic allocation, Monte Carlo simulation, and transport distance sensitivity. The scenario ranking depended on the functional unit: per Mg of waste, the sawdust substrate was lowest (39.75 kg CO₂eq), whereas, per kg of protein, the bran substrate was best (8.87 kg CO₂eq, ~66% below bakery waste). Electricity, additive, and starter diet dominated the footprint. The conditioning additive, not the waste itself, governed sustainability; the bran–bakery waste difference was statistically discernible. Full article

The use of crossbreeding between dairy and beef breeds has been adopted as a strategy to add value to male calves from dairy systems, improve productive efficiency, and reduce economic and animal welfare concerns. This study evaluated the effects of Holstein × Angus crossbreeding on productive performance, metabolism, ruminal fermentation, nutrient digestibility, carcass characteristics, meat quality, and fatty acid profile during the feedlot finishing phase. Twenty-four uncastrated male cattle (8 Holstein, 8 Angus, and 8 crossbreds) were confined for 130 days and fed an isoenergetic and isonitrogenous diet. No significant differences were observed among breeds for weight gain, dry matter intake, feed efficiency, or nutrient digestibility (p > 0.05). However, Angus and crossbred cattle showed higher carcass yield compared to Holstein cattle (p ≤ 0.05). Angus and crossbred animals presented higher concentrations of total volatile fatty acids, acetate, and propionate in the rumen (p ≤ 0.05). Breed differences were also observed in erythrocyte indices and serum urea concentrations (p ≤ 0.05). Meat from crossbred animals showed superior quality attributes compared to Holstein, including lower ultimate pH, higher lightness, greater water-holding capacity, and an intermediate lipid profile between the parental breeds (p ≤ 0.05). It is concluded that Holstein × Angus crossbreeding improves carcass yield, ruminal fermentation efficiency, and meat quality, without compromising productive performance, representing a viable strategy for adding value to male calves from dairy herds under tropical production conditions. Full article

Agricultural by-products and Chinese medicine crop residues, as non-traditional animal feed, have great potential to alleviate the scarcity of traditional feed and reduce the environmental burden. In this study, the effects of adding fermented ginseng by-products to the diet on growth performance, meat quality, flavor characteristics and metabolism of Hongyu roosters were evaluated. A total of 100 Hongyu roosters were randomly assigned to either a control (Con) group fed a basal diet or a fermented ginseng by-products (Fe) group fed a basal diet supplemented with 3% fermented ginseng by-products, with five replicates per group, for 100 days. The results demonstrated that the fermented diet significantly enhanced final body weight and average daily gain (ADG) while reducing the feed conversion ratio (FCR) (p < 0.05). The percentages of breast and thigh muscles and breast muscle fiber diameter were significantly increased. The results also exhibited enhanced water-holding capacity, coupled with significantly decreased shear force and drip loss (p < 0.05). Electronic nose and tongue analyses confirmed enriched meat aroma and optimized taste profiles, which aligned with elevated levels of flavor-precursor amino acids and essential polyunsaturated fatty acids. Serum metabolomics found purine metabolism and the biosynthesis of unsaturated fatty acids to be pivotal pathways. Metabolites related to nucleotide and lipid metabolism were regulated. In conclusion, fermented ginseng by-products serve as an effective functional feed to improve poultry growth performance and meat quality. Full article

The ruminal epithelium plays a central role in nutrient absorption, epithelial barrier function, and mucosal immune defense. However, the molecular mechanisms by which dietary Perilla frutescens seeds (PFS) regulate ruminal epithelial immunity remain poorly understood. This study investigated the transcriptomic responses of the sheep ruminal papilla to dietary PFS supplementation. Forty-five male Tan sheep were assigned to three dietary treatments (n = 15 per group): a low-concentrate diet (LC), a high-concentrate diet (HC), and the LC diet supplemented with 3% PFS (LC + PFS). After an 84-day feeding trial, ruminal papilla tissues from six animals per group were randomly subjected to RNA sequencing and integrated bioinformatic analyses, covering all three pairwise comparisons (LC vs. HC, HC vs. LC + PFS, and LC vs. LC + PFS). The LC vs. LC + PFS comparison served as the direct assessment of PFS effects under the same basal diet, whereas HC vs. LC + PFS was treated as a cross-dietary comparison. LC vs. HC yielded 387 differentially expressed genes (DEGs), HC vs. LC + PFS yielded 104 DEGs, and LC vs. LC + PFS yielded 33 DEGs, with predominant enrichment in metabolic and stress-adaptive pathways (AMPK, MAPK, PI3K-Akt). The latter were mainly associated with metabolic and structural pathways. Propionate and valerate were negatively correlated with several interferon-signaling and antigen-presentation genes. Collectively, the direct LC vs. LC + PFS comparison demonstrates that PFS supplementation under physiological conditions is associated with targeted metabolic modulation. Meanwhile, the cross-dietary HC vs. LC + PFS comparison reveals that, relative to high-concentrate feeding, the PFS-supplemented low-concentrate feeding regimen is transcriptionally associated with enhanced immune surveillance capacity in a non-inflammatory manner. These findings provide transcriptomic evidence supporting the potential of PFS as a modulator of ruminal epithelial homeostasis and offer a foundation for further investigation into its application as a functional feed ingredient. Full article

This study focused on dietary supplementation with flaxseed in fattening pigs to observe health benefits and important biological findings, including cell membrane integrity, proliferation, and angiogenesis. Animals received flaxseed for 6 or 3 weeks prior to slaughter. Pigs were divided into a control group (standard diet) and experimental groups F6 (6 weeks) and F3 (3 weeks), which received flaxseed in the feed. Spectroscopy followed by an electrophoretic method was used to study the levels of basic biochemical parameters, including LDH. Subsequently, gas chromatography revealed fatty acid concentrations in the pigs’ livers, and finally, immunohistochemical analysis was used to detect CD31 and PCNA antigens in the liver and jejunum. The highest weight gain was measured in the F6 group. After slaughter, blood samples revealed a decreased glucose level in the F6 group, maintained levels of basic biochemical parameters, and decreased concentrations of LDH in blood, heart, liver, and skeletal muscle extracts, thus improving cell membrane integrity. A long-term supplementation period led to better utilization of essential fatty acids, an improved n-6:n-3 ratio, and other atherogenic indices related to cardiovascular health. Flaxseed also affected the expression of CD31 and PCNA proteins in the liver and jejunum, mainly in the F6 group. Full article

Background: In patients with atrial fibrillation receiving long-term anticoagulation therapy with dabigatran etexilate (DABE), moxifloxacin (MFLX) is frequently coadministered to treat concurrent infections; however, the potential drug–drug interaction (DDI) between these agents remains unclear. Herein, we examined the underlying mechanism by which MFLX attenuates DABE pharmacokinetics in rats; subsequently, we elucidated the DDI in humans by establishing a physiologically based pharmacokinetic (PBPK) model based on these animal data. Methods: The 3- and 14-day effects of 40 mg/kg MFLX once daily and secondary bile acid (SBA)-containing dietary intervention on the pharmacokinetic profile of DABE and its active form, dabigatran (DAB), were examined in a rat model. Ileum tissues were harvested to measure the expression of P-glycoprotein (P-gp), pregnane X receptor (PXR), and peroxisome proliferator-activated receptor alpha (PPARα). In addition, we examined the effects of secondary bile acids (SBAs) on P-gp expression and quantified P-gp-mediated DABE efflux transport activity in Caco-2 cells. A PBPK model was used to predict the risk of DAB exposure under this DDI scenario and under combined high-risk conditions, including renal impairment and advanced age. Results: Treatment with MFLX for 3 and 14 days inhibited SBA-producing gut microbiota, thereby suppressing the conversion of primary bile acids to SBAs. Concurrently, a marked reduction in intestinal P-gp expression was observed, along with a significant enhancement of the oral bioavailability of DABE. These effects were reversed by SBA-containing diets. In vitro experiments using Caco-2 cells revealed that physiologically relevant concentrations of SBA significantly upregulated P-gp expression and function, whereas MFLX incubation alone showed no direct modulatory effect on these transporters or regulators. PBPK simulation results showed that in vivo exposure of DAB would increase by 41.7%, 104%, 251%, and 115% when coadministered with MFLX alone, with coexisting mild renal impairment, moderate renal impairment, and aging, respectively. Conclusions: MFLX increases DAB exposure by reducing SBA-regulated intestinal P-gp function. PBPK simulations suggest a low risk of DDI from MFLX coadministration alone; however, caution is warranted in patients with aging or renal impairment. Full article

Background: Large yellow tea (LYT), a distinctive variety made from mature leaves, has recently gained attention for its remarkable health benefits. However, whether these benefits can be transmitted from mother to offspring remains unexplored. Purpose: This study investigated whether maternal LYT consumption confers intergenerational protection against metabolic and behavioral disorders induced by perinatal bisphenol A (BPA) exposure in F1 offspring. Methods: A mouse model of perinatal BPA exposure (0.03% in diet) was established with or without maternal LYT supplementation (2.5% in diet). Metabolic parameters were assessed through biochemical assays and gene expression analysis (RT-PCR). Energy expenditure and spontaneous activity were monitored using a Comprehensive Lab Animal Monitoring System (CLAMS). Hippocampal proteomic profiling was performed using label-free quantitative proteomics. Results: LYT significantly reduced maternal BPA body burden, potentially via limiting absorption, enhancing glucuronidation metabolism, and promoting excretion. Notably, LYT exhibited bidirectional metabolic regulation, alleviating gestational hyperglycemia in dams while restoring hypoglycemia in offspring, and normalizing underweight and hypolipidemia. Mechanistically, the SIRT6 (sirtuin 6)/FOXO1 and SIRT6/SREBP1 pathways may be involved in regulating gluconeogenesis and lipogenesis. Concurrently, LYT rectified BPA-induced hyperactivity and reduced excessive energy expenditure. Proteomic analysis revealed that LYT partially restores BPA-induced dysregulation of cholesterol metabolism and glutamatergic/GABAergic synaptic pathways, which may contribute to rebalancing synaptic homeostasis. Conclusions: These findings suggest that maternal LYT supplementation confers intergenerational protection against BPA-induced metabolic and behavioral disorders in mice, potentially acting through enhanced toxin clearance, bidirectional metabolic regulation, behavioral normalization, and partial restoration of hippocampal synaptic homeostasis. This study provides a theoretical basis for developing natural dietary interventions to mitigate developmental toxicant-induced health risks. Full article

Aqueous Chlorella extract (CE) is a functional feed additive derived from widely cultivated microalgae. It is rich in proteins, polysaccharides, pigments, polyunsaturated fatty acids, vitamins and other bioactive compounds. CE possesses great potential to improve the health status and physiological performance of aquatic animals. This study investigated the effects of dietary CE on inflammatory response, non-specific immunity, antioxidant capacity, lipid metabolism, immune gene expression, intestinal histomorphology and intestinal microbiota in Litopenaeus vannamei. Shrimp were fed diets containing 0%, 1%, or 5% CE for 60 days. The 1% CE treatment produced stronger responses in several non-specific immune and antioxidant-related indicators and induced broader changes in immune-related gene expression. In contrast, the 5% CE treatment showed more pronounced changes in inflammation-related factors, lipid metabolism, and intestinal morphology. CE supplementation also altered intestinal microbial composition and predicted microbial functions, with different response patterns between the two inclusion levels. A distinctive feature of this study is the integrated identification of inclusion-level-specific response patterns across host physiological and intestinal microbial endpoints, rather than a simple increase in effects with increasing CE inclusion. Overall, the 1% treatment was more closely associated with immune and antioxidant-related responses, whereas the 5% treatment was more closely associated with anti-inflammatory, lipid-regulatory, and intestinal effects. These findings demonstrate the potential of CE as a functional aquafeed additive for improving aquatic animal health and provide a scientific basis for its application in sustainable shrimp aquaculture. Full article

Livestock farming is blamed for its significant carbon footprint (CF), contributing to environmental pollution and climate change. Among other approaches, this has highlighted the need to find alternative feeding systems for cattle production that are potentially able to reduce greenhouse gas (GHG) emissions. In this context, the objective of the present study was to compare the CF of producing cattle fed a Conventional diet versus cattle fed a diet that included vegetable by-products (VBP diet) sourced from the local agri-food industry. In this study, twenty-four entire male young bulls were reared in Navarra, Spain. Twelve calves were finished on the VBP diet that also included fodder and grain, and the remaining animals were finished with a local Conventional diet based on concentrate and straw. Results showed a larger CF of meat from animals fed the Conventional diet in comparison with the VBP-fed ones, that is, 117.84 kg versus 42.01 kg of CO₂ equivalent per kilogram of meat, respectively. This research demonstrates that using by-products from the local agri-food industry for feeding cattle has an important beneficial effect on the environment. It is not only a circular economy solution that recovers and recycles by-products instead of treating them as waste, but can also notably reduce the GHG associated with livestock production. This study marks the beginning of ongoing research into the effect of introducing regional vegetable by-products in the diet of livestock and their corresponding impacts on productivity and the environment, particularly in terms of GHG emissions per kilogram of feed consumed. Full article

With the aim of evaluating the effects of combining a natural additive composed of a blend of essential oils plus vitamin D3 (EOD3) with Bacillus subtilis (BS) or with the antibiotic virginiamycin (VM) on growth-performance and carcass traits of finishing lambs subjected to high ambient heat load, 48 intact male lambs (initial weight = 33.71 ± 3.21 kg) were used in a feeding trial lasting 61 d. Treatments consisted of supplementing (as a feed basis) a total mixing finishing diet (90:10 concentrate-to-forage ratio) as follows: (1) without feed additives (Control); (2) supplemented with EOD3 (a blend of 100 mg essential oils plus 0.10 mg vitamin D3/kg diet); (3) diet supplemented with EOD3 plus 2 g Bacillus subtilis PB6/kg diet to provide 2.2 × 10⁸ CFU (EOD3+BS); and (4) basal diet supplemented with EOD3 plus 25 mg virginiamycin/kg diet (EOD3+VM). The temperature–humidity index (THI) during the experiment averaged 82.52 ± 1.10. Compared to non-supplemented lambs, lambs that received EOD3 alone showed greater (p < 0.03) average daily gain (ADG; 15.3%), gain-to-feed ratio (GF; 12.3%), and observed-to-expected dietary NE ratio (5.9%). The combination of EOD3 with BS resulted in identical ADG but a numerically larger DMI (7.1%, p = 0.087) than the EOD3 treatment, leading to lower (p = 0.024) GF and a lower (p < 0.01) observed-to-expected dietary NE ratio. In contrast to our expectation, combining VM and EOD3 did not increase growth response (p = 0.69), GF (p = 0.49), or dietary energy utilization efficiency (p = 0.09) when compared to EOD3 alone. Because the lambs that received supplemental EOD3 alone and their combinations showed greater final weight, hot carcass weight was heavier than in controls; however, no effects were observed on the other carcass variables evaluated, including whole cuts and shoulder tissue composition. Lambs that received EOD3 and their combinations showed a lower relative intestinal mass than controls (p < 0.04). This result confirms the role of EOD3 as a tool to minimize the negative impact of high ambient temperature on the performance of fattening lambs. Combining EOD3 with Bacillus subtilis or with VM did not improve energy utilization efficiency or carcass traits compared with EOD3 supplementation alone in lambs fattening under high ambient heat load. Further research is needed to better understand the interactions among different additives and to propose more effective supplementation strategies in animals subjected to different environmental conditions. Full article

Beef is an excellent source of protein in the human diet; however, high production levels in the livestock industry expose meat products to a greater risk of contamination by bacteria such as Escherichia coli, a pathogen of great significance in public health due to its widespread distribution and multidrug-resistance (MDR). Therefore, the objective of this study was to analyze the phenotypic and genotypic antimicrobial resistance (AMR) in E. coli isolated from raw beef through a systematic review and meta-analysis. A total of 24 articles were selected for this study; in the phenotypic evaluation, 9356 observations were reported with a pooled prevalence ratio for AMR of 0.49. Additionally, 44 antibiotics were reported, with ampicillin (0.60), tetracycline (0.59), and sulfamethoxazole/trimethoprim (0.51) having the highest frequency of use in the evaluation of the resistance profile of E. coli. Resistant genes showed a pooled prevalence ratio of 0.42; the bla (0.33), tet (0.42) and sul (0.48) genes were particularly notable for their association with AMR in the strains. The analyzed data on MDR provides valuable information for monitoring E. coli to help in the health management of this pathogen that affects human and animal health worldwide. Full article

Persistent racial and ethnic disparities in type 2 diabetes mellitus (T2DM) are incompletely explained by genetic susceptibility, obesity, lifestyle, and socioeconomic factors, suggesting that additional biological mechanisms may link environmental exposures to metabolic disease risk. Increasing evidence indicates that the exposome, encompassing environmental exposures across the life course, may influence long-term metabolic health through molecular mechanisms that integrate environmental signals with host biology. This Review synthesizes epidemiological, experimental, and mechanistic evidence on the gut microbiota–host epigenetic axis and its potential role in linking environmental exposures to population differences in T2DM susceptibility. Gut microbial dysbiosis alters the production and metabolism of short-chain fatty acids, bile acids, and tryptophan-derived metabolites. These microbial metabolites can modulate host signaling and epigenetic processes, including DNA methylation, histone modifications, and non-coding RNA activity, which may influence the expression of genes involved in glucose homeostasis, inflammation, and insulin sensitivity. Conversely, host epigenetic programs may influence intestinal barrier integrity and immune responses, thereby potentially affecting the gut microbial ecosystem, highlighting the reciprocal nature of host–microbiota interactions. We further examine how diet, psychosocial stress, environmental pollutants, and socioeconomic conditions may shape the microbiota–epigenetic axis across diverse populations, providing a framework for understanding differences in metabolic susceptibility without attributing disparities to intrinsic biological variation. However, direct human evidence linking the gut microbiota–host epigenetic axis to racial and ethnic disparities in T2DM risk remains limited, and much of the current framework is based on mechanistic studies, animal models, and associative human data rather than direct causal evidence. Further research in diverse human populations is needed to validate these pathways and establish their contribution to T2DM disparities. This framework may inform biomarker discovery, stratification, precision nutrition, and microbiome-targeted interventions and generate hypotheses for equitable prevention and personalized management of T2DM across diverse populations. Full article

Insulin resistance (IR) represents one of the most pressing problems in contemporary public health. Its estimated global prevalence ranges from approximately 15.5% to over 61%, depending on the population studied, the diagnostic criteria applied, and the method used for its assessment. Despite the scale of the problem, IR remains underrecognized and lacks formal definition as a distinct disease entity, even as a growing number of clinicians and researchers worldwide describe it as such. Its asymptomatic or mildly symptomatic course allows it to remain undetected for years, during which it makes a significant contribution to the development of type 2 diabetes, cardiovascular disease (CVD) and metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD), and has been increasingly linked to cellular senescence, certain cancers, neuropsychiatric disorders, and other metabolic conditions. The aim of this review was to summarize current knowledge on the pathophysiology, diagnosis, and clinical implications of insulin resistance, to discuss current challenges in its diagnosis, and to evaluate whether available scientific evidence supports its recognition as a distinct disease entity. This narrative review is based on clinical, epidemiological, and mechanistic data retrieved from PubMed and Google Scholar. Meta-analyses, systematic reviews, clinical and observational studies, clinical guidelines, and expert position statements were analyzed. Animal studies were excluded to maintain a focus on human public health implications. The diagnostic gold standard—the hyperinsulinemic-euglycemic clamp—was discussed, along with surrogate methods used in clinical practice (HOMA-IR, OGTT with insulin measurements, the TyG index, and the TG/HDL-C ratio). Factors potentially contributing to the pathogenesis of IR were examined, including hyperinsulinemia (HI), high-carbohydrate diets, inflammation, stress, and sleep disturbances, as well as conditions in which IR occurs physiologically. The findings indicate that current evidence supports the need for a clearer clinical and diagnostic framework for insulin resistance and suggest that its recognition as a distinct disease entity could facilitate earlier diagnosis, improve the standardization of clinical management, and enable earlier metabolic intervention. Given the steadily rising prevalence of metabolic disease, systemic efforts directed at the early identification and treatment of IR may be a key component of strategies aimed at reducing the population-level burden of metabolic disease and its negative consequences. Full article