Search Results (366)

Heat stress (HS) is a major environmental factor negatively impacting the reproductive performance of livestock. This study investigates the molecular mechanisms of heat stress on the hypothalamic–pituitary–ovarian (HPO) axis in Hu sheep. A heat-stressed animal model was established, and high-throughput RNA sequencing (RNA-seq) was employed to analyze gene expression in the hypothalamus, pituitary, and ovarian tissues of both control and heat-stressed groups. The results revealed significant changes in estrus behavior, hormone secretion, and reproductive health in heat-stressed sheep, with a shortened estrus duration, prolonged estrous cycles, and decreased levels of FSH, LH, E₂, and P4. A total of 520, 649, and 482 differentially expressed genes (DEGs) were identified in the hypothalamus, pituitary, and ovary, respectively. The DEGs were enriched in pathways related to hormone secretion, neurotransmission, cell proliferation, and immune response, with significant involvement of the p53 and cAMP signaling pathways. Tissue-specific responses to heat stress were observed, with distinct regulatory roles in each organ, including GPCR activity and cytokine signaling in the hypothalamus, calcium-regulated exocytosis in the pituitary, and cilium assembly and ATP binding in the ovary. Key genes such as SYN3, RPH3A, and IGFBP2 were identified as central to the coordinated regulation of the HPO axis. These findings provide new insights into the molecular basis of heat stress-induced impairments in reproductive function—manifested by altered estrous behavior, reduced hormone secretion (FSH, LH, E₂, and P4), and disrupted gene expression in the hypothalamic–pituitary–ovarian (HPO) axis—and offer potential targets for improving heat tolerance and reproductive regulation in sheep. Full article

Over the past decades, bile acids have been recognized as important signaling molecules with significant roles in metabolic health and disease. Many of their beneficial effects are mediated through the activation of the Takeda G protein-coupled receptor 5 (TGR5), a G protein-coupled receptor ubiquitously expressed in both humans and animals. Upon activation, TGR5 stimulates adenylate cyclase, leading to increased cyclic adenosine monophosphate (cAMP) levels and subsequent activation of protein kinase A (PKA). PKA then phosphorylates and activates several downstream signaling pathways, including exchange protein directly activated by cAMP (EPAC), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein kinase B (AKT). Through these pathways, TGR5 acts as a key molecular link between bile acid signaling and the regulation of energy metabolism. TGR5 activation has been associated with body weight loss in obese models, primarily by reducing food intake, enhancing thermogenesis in adipose tissue and muscle to increase energy expenditure, and improving insulin secretion. This review highlights recent advances in our understanding of TGR5 biology and critically examines its therapeutic potential, limitations, and controversies in the context of energy metabolism, offering new perspectives and opportunities for treating metabolic disorders. Full article

The intersection of microbial food safety and antimicrobial resistance (AMR) represents a mounting global threat with profound implications for public health, food safety, and sustainable development. This review explores the complex pathways through which foodborne pathogens—such as Salmonella spp., Escherichia coli (E. coli), Listeria monocytogenes (L. monocytogenes), and Campylobacter spp.—acquire and disseminate resistance within human, animal, and environmental ecosystems. Emphasizing a One Health framework, we examine the drivers of AMR across sectors, including the misuse of antibiotics in agriculture, aquaculture, and clinical settings, and assess the role of environmental reservoirs in sustaining and amplifying resistance genes. We further discuss the evolution of surveillance systems, regulatory policies, and antimicrobial stewardship programs (ASPs) designed to mitigate resistance across the food chain. Innovations in next-generation sequencing, metagenomics, and targeted therapeutics such as bacteriophage therapy, antimicrobial peptides (AMPs), and CRISPR-based interventions offer promising alternatives to conventional antibiotics. However, the translation of these advances into practice remains uneven, particularly in low- and middle-income countries (LMICs) facing significant barriers to diagnostic access, laboratory capacity, and equitable treatment availability. Our analysis underscores the urgent need for integrated, cross-sectoral action—anchored in science, policy, and education—to curb the global spread of AMR. Strengthening surveillance, investing in research, promoting responsible antimicrobial use, and fostering global collaboration are essential to preserving the efficacy of existing treatments and ensuring the microbiological safety of food systems worldwide. Full article

Skin and soft tissue infections (SSTIs) are becoming an urgent public health issue worldwide. The globe is facing a growing problem with drug-resistant germs, and current treatments are not quite cutting it. There is a real need for new therapies that can tackle these challenges more effectively. This brings us to an interesting question: Can extracellular vesicles (EVs) from different sources, such as mesenchymal stem cells (MSCs), immune cells, or even plants and animals, help in treating SSTIs, especially given the rise in drug resistance? Studies have shown that MSC-derived EVs are particularly noteworthy because they carry components such as antimicrobial peptides (AMPs) that can work together to fight infections, boost the immune response, and aid in healing. These vesicles play a role in how our body interacts with infections, helping to clear bacteria, reduce inflammation, and promote tissue repair. We also see that EVs from plants and bacteria can directly fight off germs, while those from animals can support the healing process of skin. Although early studies have shown promise for EV therapies, there are still hurdles to overcome, such as ensuring consistent production and delivery. This review looks at the potential of EVs as powerful agents in managing infections and supporting healing, highlighting an exciting area of research in medicine. Full article

Herpes simplex virus type 1 (HSV-1) is a globally prevalent pathogen that can infect a variety of animal species as well as humans. However, existing antiviral therapies are constrained in their capacity to effectively target viral latency and prevent recurrent infections. Antimicrobial peptides (AMPs), particularly cathelicidins, as part of innate immune system have demonstrated broad-spectrum efficacy against viral pathogens. In this study, four peptides derived from Elephas maximus cathelicidin EM were designed and optimized (EM-1 to EM-4). We identified low toxicity peptide derivatives through hemolytic and cytotoxicity assays, quantified their anti-HSV-1 activity by determining IC₅₀. Antiviral mechanisms were investigated using RT-qPCR and antiviral efficacy was ultimately validated in C57BL/6J mice through viral load quantification in brain, lung, and heart tissues. Our findings revealed that EM-1 significantly inhibited HSV-1 replication in U251 cells. In a murine footpad inoculation model, EM-1 administration substantially reduced viral loads and alleviated inflammatory responses. Histological assessment demonstrated that EM-1 treatment mitigated HSV-1 induced tissue damage in infected mice. We also found that EM-1 exerted its antiviral effects by upregulating the expression of interferon-gamma and its downstream genes, such as ISG15 and MX1. These findings indicated that EM-1 is a dual function peptide that inhibits replication of HSV-1 as well as enhances host antiviral immunity. Collectively, this study highlights the therapeutic potential of elephant cathelicidin derived peptides in antiviral development. Full article

Neurodegenerative disorders, mental conditions, and cognitive decline represent significant challenges worldwide, with growing pieces of evidence implicating alterations in neurotrophin signaling as central to these diseases. Neurotrophins—such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)—are indispensable for neuronal survival, differentiation, and synaptic plasticity, and their dysregulation is closely associated with various neuropathological situations. Similarly, dietary plant polyphenols, abundant in vegetables, fruits, wine, tea, and extra virgin olive oil, show powerful anti-inflammatory, antioxidant, and anti-apoptotic activities. This narrative review critically addresses the evolving body of evidence that links plant polyphenols and brain neurotrophins, emphasizing several molecular mechanisms by which polyphenols regulate and modulate neurotrophin signaling. Crucial pathways include mitigation of neuroinflammatory responses, activation of intracellular cascades such as the cAMP response element-binding protein (CREB), epigenetic modulation, and the diminution of oxidative stress. Together, these effects contribute to potentiated enhanced synaptic function, neuronal integrity, and better learning and memory processes. Moreover, this narrative review examines how polyphenol-induced upregulation of neurotrophins may alleviate conditions associated not only with neurodegeneration but also with addiction and mood disorders, suggesting extensive therapeutic approaches. Findings from clinical investigations and animal models are presented to sustain the neuroprotective role of polyphenol-rich diets. Lastly, future research directions are recommended, focusing on polyphenol bioavailability optimization, considering combinatory dietary stratagems, and proposing personalized nutritional interventions. This wide-ranging perspective highlights plant polyphenols as encouraging modulators of neurotrophin pathways and supports their inclusion in approaches aimed at promoting brain health and counteracting neurodegenerative decline. Full article

Staphylococcus aureus is an important cause of food intoxication, which has the potential to induce diverse infections, toxinoses and life-threatening diseases among humans and animals. This study investigated the prevalence, antimicrobial resistance, and genetic diversity of S. aureus and methicillin-resistant S. aureus (MRSA) in retail raw meat from Shandong (March 2021–October 2022). The distribution of virulence genes, antimicrobial susceptibility, and genetic diversity of these isolates were analyzed. From a total of 442 samples, 87 (19.7%) S. aureus and 11 (2.5%) MRSA were isolated. According to the antimicrobial susceptibility testing, it was found that all the S. aureus isolates were resistant to at least one antimicrobial. Most isolates (95.9%) were resistant to penicillin, with high resistance to ampicillin (82.7%) and multidrug resistance in 76.5% of cases. One isolate could simultaneously resist eleven antimicrobials (ERY-CLI-GEN-SMZ-FFC-PEN-PRL-AMC-CIP-TET-AMP). In contrast, all the isolates showed sensitivity to vancomycin. The most prevalent virulence gene was sed, accounting for 10.2%, followed by sec (8.2%). Regarding genetic polymorphism, these isolates were divided into 21 different sequence types (STs) using multilocus sequence typing (MLST) and 33 staphylococcal protein A (spa) types using spaTyper 1.0 tool. The most prevalent sequence types were ST398 (22.4%), followed by ST7 (20.4%), while ST59, ST1, ST188, ST9, ST398, and ST7 were observed in MRSA isolates. The most prevalent spa types were t034 (15.3%), followed by t899 (10.2%), while t441, t127, t184, t899, t034, and t091 were observed in MRSA isolates. In conclusion, our study highlights the high prevalence of S. aureus and MRSA in different retail raw meats in Shandong. This poses a potential threat to food safety and underscores the need for enhanced surveillance and stricter antibiotic control measures. Full article

Background/Objectives: The rise of antibiotic-resistant bacteria presents a major global health challenge, highlighting the need for novel antimicrobial agents such as antimicrobial peptides (AMPs). AMPs are promising due to their broad-spectrum activity, membrane-disruptive mechanisms, and low development of resistance. This study aimed to design and evaluate novel AMPs derived from a synthetic parent peptide (PEP-38). Methods: Novel peptides were designed using bioinformatics tools, including CAMP_R3 and Peptide Ranker. Their antimicrobial potential was validated through in vitro assays, including bacterial susceptibility, antibiofilm activity, cytotoxicity, hemolysis, and time–kill kinetics. Results: Among the designed peptides, Hel-4K-12K showed potent activity against both Gram-positive and Gram-negative bacteria, with MICs ranging from 3.125 to 6.25 µM. It also effectively eradicated biofilms of resistant Staphylococcus aureus at an MBEC of 6.25 µM. Time–kill assays confirmed rapid bactericidal action, achieving complete bacterial elimination within one hour at its MIC. Moreover, Hel-4K-12K exhibited low toxicity toward mammalian MDCK cells (>82% viability at MIC) and minimal hemolytic activity on human erythrocytes. Conclusions: Hel-4K-12K demonstrates strong antibacterial and antibiofilm activities with a favorable safety profile, indicating its potential as a therapeutic candidate for treating infections caused by resistant bacteria. These findings support further development of this peptide as a basis for new antimicrobial drug strategies. In addition to its promising in vitro profile, future studies will investigate Hel-4K-12K in animal models and evaluate strategies for attaining stable formulations, such as peptide encapsulation or PEGylation. These steps are critical to ensure its therapeutic viability in systemic applications. Full article

Background/Objectives: The widespread use of antibiotics in animal husbandry has led to an increase in antimicrobial-resistant Escherichia coli, particularly strains producing extended-spectrum β-lactamases (ESBL) and AmpC β-lactamases. This study aimed to isolate and characterize such strains from fecal samples of broiler chickens (n = 71) and slaughtered turkeys (n = 31) in northwestern Romania. Methods: Antimicrobial susceptibility testing and PCR were used to evaluate phenotypic resistance patterns and detect the presence of resistance genes (AmpC, blaZ, and blaTEM). Results: The results showed that 55% of turkey and 61% of broiler isolates were presumptive ESBL/AmpC producers. Among all isolates, 50% were classified as extensively drug-resistant (XDR), 44% as multidrug-resistant (MDR), and only 6% were fully susceptible. Gene detection revealed an overall prevalence of 44.2% for AmpC, 72.7% for blaZ, and 58.1% for blaTEM, yielding a total penetrance of 51.09%. The diagnostic odds ratio (DOR) values, ranging from 0.67 to 81, suggest the efficacy of the antibiotic susceptibility testing method used in detecting the presence of these resistance genes. Conclusion: Overall, these findings highlight a significant burden of antimicrobial-resistant, poultry-associated E. coli strains, warranting stricter antimicrobial stewardship. Full article

Follicle stimulating hormone (FSH) stands as one of the most prevalently used reproductive hormones in the field of animal-assisted reproduction. Conventionally, pituitary FSH is sourced from the heterologous pituitary glands of pigs and sheep procured from slaughterhouses, and it typically exists in the form of crude FSH. The specific challenges inherent in FSH-based assisted reproduction drugs has significantly spurred the interest in exploring novel alternatives, aiming to reduce the reliance on these traditional sources in relevant production processes. In this study, the α- and β-FSH genes were retrieved from pituitary cDNA libraries. These genes were selected to construct a recombinant protein—the novel cow recombinant FSH (CrFSH)—through the application of the homologous recombination method. Notably, the β-subunit was extended by a carboxy-terminal peptide (CTP). After successfully integrating the two genes into Chinese hamster ovary (CHO) cells, the recombinant protein (approximately 33 kDa) in the culture supernatant was detected using Western blotting (WB). The results of the GCs proliferation experiment indicated that both 1.2 µg/mL pFSH and 20–20,000 ng/mL CrFSH could significantly promote the proliferation of GCs in vitro. Remarkably, on the 4th day after treatment, 20 ng/mL of CrFSH had a higher GCs proliferation rate than 1.2 μg/mL of pFSH (p < 0.001). Additionally, cyclic adenosine monophosphate (cAMP) induction assay in GCs unequivocally confirmed that CrFSH possesses superior activity compared to pFSH. These findings underscore that this recombinant protein holds great potential as a promising candidate for FSH production in assisted reproduction approaches for dairy herds. Full article

Antibiotic resistance is increasing at an alarming rate worldwide, in large part due to their misuse and improper disposal. Antibiotics administered to treat human and animal diseases, including feed supplements for the treatment or prevention of disease in farm animals, have contributed greatly to the emergence of a multitude of antibiotic-resistant pathogens. Shewanella is one of many bacteria that have developed antibiotic resistance, and in some species, multiple-antibiotic resistance (MAR). Shewanella is a rod-shaped, Gram-negative, oxidase-positive, and H₂S-producing bacterium that is naturally found in the marine environment. In humans, Shewanella spp. can cause skin and soft tissue infections, septicemia, cellulitis, osteomyelitis, and ear and wound infections. Some Shewanella have been shown to be resistant to a variety of antibiotics, including beta-lactams, aminoglycoside, quinolones, third- or fourth-generation cephalosporins, and carbapenems, due to the presence of genes such as the bla_OXA-class D beta-lactamase-encoding gene, bla_AmpC-class-C beta-lactamase-encoding gene, and the qnr gene. Bacteria can acquire and transmit these genes through different horizontal gene-transmission mechanisms such as transformation, transduction, and conjugation. The genes for antibiotic resistance are present on Shewanella chromosomes and plasmids. Apart from this, heavy metals such as arsenic, mercury, cadmium, and chromium can also increase antibiotic resistance in Shewanella due to co-selection processes such as co-resistance, cross resistance, and co-regulation mechanisms. Antibiotics and drugs enter Shewanella spp. through pores or gates in their cell wall and may be ejected from the bacteria by efflux pumps, which are the first line of bacterial defense against antibiotics. Multiple-drug resistant Shewanella can be particularly difficult to control. This review focuses on the phenotypic and genomic characteristics of Shewanella that are involved in the increase in antimicrobial resistance in this bacterium. Full article

At the present stage, heavy metal pollution, led by environmental exposure to cadmium (Cd), has caused incalculable losses in animal husbandry. The potential value of caprylic acid as a medium- and long-chain fatty acid with a unique role in regulating lipid metabolism has attracted much attention. Our previous study found that octanoic acid levels were significantly reduced under Cd-exposed conditions in Hu Sheep, on the basis of which we investigated the protective effect of sodium octanoate, a derivative of octanoic acid, against Cd exposure in Hu Sheep in the present study. In this study, an animal model of Cd exposure in Hu Sheep was established. Comprehensive assessment of Cd-induced intestinal injury using hematoxylin and eosin (H&E) staining, immunostaining and carried out in-depth analyses combined with lipid metabolomics and transcriptomics. The results showed that Cd exposure triggered intestinal inflammation, barrier function damage and oxidative stress imbalance. Lipid metabolomics analysis showed that Cd exposure severely disrupted lipid metabolic processes, especially the glycerophospholipid metabolic pathway, suggesting that lipid metabolic disorders are closely related to intestinal injury. Notably, sodium octanoate could partially reverse the lipid metabolism abnormality by regulating the Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, effectively alleviating the Cd toxicity, which provides a brand-new prevention and control strategy for Cd-induced intestinal injury in the livestock industry pollution-mediated disease. Full article

Yeast culture is widely used in ruminants to improve gut health, immunity, and productivity; however, its impact on meat quality remains unclear. This study aimed to investigate the effects of yeast culture supplementation in the basic diet on meat quality of Small-tail Han sheep. A total of 40 Small-tail Han sheep (17.5 ± 1.2 kg) were randomly assigned to two treatment groups, with 20 sheep in each group. The sheep were fed either a basic diet (CON) or the basic diet supplemented with 1% yeast culture (YSD) for 90 days. At the end of the trial, the Longissimus dorsi muscle (LOD) of the sheep was collected for meat quality evaluation, as well as transcriptome and metabolome analyses. Meat quality data were analyzed using t-tests, while transcriptome and metabolome data were analyzed using bioinformatics tools. The results showed that YSD supplementation significantly reduced carcass fat content (p < 0.05) and increased the pH values (p < 0.05) of LOD compared to the CON group. Multi-omics analysis revealed significant changes in the levels of 349 transcripts and 149 metabolites (p < 0.05) in the YSD group relative to the CON group. These changes were primarily associated with immune response pathways and purine metabolism. Further integrated transcriptomics and metabolomics analysis identified significant alterations in the expression of adenylate kinase 4 (AK4) and ribonucleotide reductase M2 (RRM2), which influenced purine metabolites, such as ADP, GMP, 3′-AMP, 3′-GMP, dGDP, adenine, guanosine, and guanine. These metabolites were markedly upregulated in the LOD of the sheep supplemented with yeast culture. In conclusion, yeast culture supplementation improved the meat quality of Small-tail Han sheep, potentially through the enhancement of immune response and purine metabolism. These findings offer valuable insights into the molecular mechanisms underlying the effects of yeast culture on animal health and meat quality. Full article

Cell death and inflammation are key innate immune responses, but excessive activation can cause tissue damage. The NLRP3 inflammasome is a promising target for reducing inflammation and promoting recovery. Immunometabolism regulates NLRP3 responses in neurological and inflammatory diseases through cyclic nucleotide signaling. Targeting phosphodiesterases (PDEs), which hydrolyze cAMP and cGMP, offer a novel approach to mitigate inflammation. While 14 PDE inhibitors are FDA-approved, PDE10A’s role in NLRP3 inflammasome activation remains unclear. This study investigates the effects of PDE10A inhibition on inflammasome-driven inflammation using two PDE10A inhibitors, MP-10 and TP-10, in macrophage and animal models of sepsis and traumatic nerve injury. Our results show that PDE10A inhibition reduces inflammasome activation by preventing ASC speck formation and by lowering levels of cleaved caspase-1, gasdermin D, and IL-1β, which are key mediators of pyroptosis. In the sepsis model, MP-10 significantly reduced inflammation, decreased plasma IL-1β, alleviated thrombocytopenia, and improved organ damage markers. In the nerve injury model, PDE10A inhibition enhanced motor function recovery and reduced muscle atrophy-related gene expression. These findings suggest that PDE10A inhibition could be a promising therapeutic approach for inflammatory and neuromuscular injuries. Given MP-10’s established safety in human trials, Phase 2 clinical studies for sepsis and nerve injury are highly promising. Full article

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a multidrug-resistant (MDR) gram-negative bacterium frequently involved in hospital-acquired pneumonia. The infection caused by this superbug has spread quickly in health centers worldwide, leading to high mortality rates. Due to this emerging scenario, the World Health Organization has categorized CRKP as the highest-priority species for the development of new compounds. In this context, antimicrobial peptides (AMPs) stand out as prototypes for alternative antimicrobials against superbugs, including CRKP. Objectives: We aimed to describe the antibacterial effect of an AMP (LyeTx I), derived from the venom of the spider Lycosa erythrognatha, against CRKP in vitro and in a murine pneumonia model. Results: LyeTx I showed antibacterial effects against all the CRKP clinical isolates tested, with a minimum inhibitory concentration (MIC) range of 2–8 µM and a minimum bactericidal concentration (MBC) range of 2–16 µM. The microbial anionic membrane was the primary target of LyeTx I, which acts by displacing divalent cations bound to this structure in a manner similar to that of polymyxins. Notably, LyeTx I displayed significant lytic activity against mimetic membranes, indicating its potential to disrupt bacterial cell integrity. In in vivo assays, the LyeTx I peptide proved to be safe at a dose of 10 mg/kg. In addition, intraperitoneal use of LyeTx I reduced the bacterial load and inflammation in the lungs of animals infected with a hypervirulent strain of CRKP. Conclusions: These results indicate that LyeTx I is a potential prototype for the development of new antibacterials against MDR species, such as CRKP. Full article