Search Results (122)

The oral epithelium is essential for maintaining oral health and plays a key role in the onset and progression of periodontitis. It serves as both a mechanical and immunological barrier and possesses antimicrobial activity. Vitamin D₃, a hormone with known immunomodulatory functions, may influence oral epithelial responses. This study investigated the effects of two vitamin D₃ metabolites on key immunological and antimicrobial functions of oral epithelial cells, both under basal conditions and during bacterial challenge. Ca9-22 oral epithelial cells were treated with 1,25(OH)₂D₃ or 25(OH)D₃ in the presence or absence of Tannerella forsythia, Fusobacterium nucleatum, or Porphyromonas gingivalis. Inflammatory responses were assessed by measuring gene and protein expression of IL-1β and IL-8. Antimicrobial activity was evaluated via expression of LL-37, hBD-2, and hBD-3, as well as direct bacterial killing assays. Expression of epithelial integrity markers E-cadherin and ICAM-1 was also analyzed. Vitamin D₃ metabolites reduced IL-8 expression and significantly increased LL-37 expression and production in Ca9-22 cells. Both forms enhanced antimicrobial activity against all tested pathogens and modulated epithelial integrity markers. Vitamin D₃ positively regulates antimicrobial and barrier functions in oral epithelial cells, suggesting a potential role in supporting oral health and preventing periodontitis progression. Full article

Crustins are a family of cysteine-rich antimicrobial peptides (AMPs), predominantly found in crustaceans, and play important roles in innate immunity. However, among the many reported crustins, few studies have explored their immunomodulatory functions. In this study, we investigated the immune function of a type I crustin (LvCrustinIa-2) in Litopenaeus vannamei, with particular emphasis on comparing the roles of its different domains. LvCrustinIa-2 possesses cationic patchy surface and amphipathic structure, and its expression was significantly induced in hemocytes after pathogen challenge. Both the recombinant LvCrustinIa-2 (rLvCrustinIa-2) and its whey acidic protein (WAP) domain (rLvCrustinIa-2-WAP) exhibited significant inhibitory activities against the tested Gram-positive bacteria. They also showed binding affinity not only for Gram-positive bacteria but also for Gram-negative bacteria. Furthermore, rLvCrustinIa-2 induced membrane leakage and structure damage in the target bacteria. Notably, chemotaxis assays revealed that rLvCrustinIa-2 and the synthetic cysteine-rich region (LvCrustinIa-2-CR) significantly enhanced the chemotactic activity of shrimp hemocytes in vitro. Knockdown of LvCrustinIa-2 triggered significant transcriptional activation of genes involved in calcium transport, inflammation, redox regulation, and NF-κB pathway. Taken together, these findings elucidate the distinct roles of the cysteine-rich region and WAP domain in type Ia crustin and provide the first evidence of a crustacean AMP with chemotactic and immunomodulatory activities. Full article

Porcine intestinal mucosa hydrolysates (PIMHs) are by-products of heparin production obtained through a specific enzymatic hydrolysis process, which can theoretically generate bioactive peptides (BAPs). This study aimed to identify, characterize, and quantify BAPs in two Palbio products manufactured by Bioiberica S.A.U. (Palafolls, Spain), which are PIMH protein sources used for animal feed: Palbio^® HP (PHP) and Palbio^® 62 SP^® (P62). Using mass spectrometry (MS)-based peptidomics, we analyzed three samples from each product, fractionated based on molecular weight (<3 kDa, 3 to 10 kDa, and >10 kDa). The <3 kDa fraction was analyzed directly, while the other two fractions were enzymatically digested before MS analysis. The workflow identified 961 peptides in PHP and 1134 in P62. Subsequent bioinformatic analysis using public databases (APD2, StraPep, AHTPDB, and BIOPEP-UWM) led to the identification of six significant BAPs in both PHP and P62, with respective quantified amounts (pg peptide/μg sample): DAVEDLESVGK (0.1626, 0.1939), EGIPPDQQRLIFAGK (0.2637, 0.1852), TITLEVEPSDTIENVK (0.3594, 0.4327), TNVPRASVPDGFLS (1.4596, 0.1898), TNVPRASVPDGFLSEL (8.0500, 0.9224), and VHVVPDQLMAF (0.0310, 0.0054). The first three BAPs are related to antimicrobial activity, while the latter three are associated with cytokine/growth factor-like, antioxidant, and immunomodulatory activities. These bioactivities align with previously reported in vivo benefits observed in animal nutrition using Palbio products. Our findings demonstrate that PHP and P62 are valuable sources of BAPs, supporting their potential role in improving animal health and performance. Full article

The Steinernema carpocapsae nematode is known to release several excretory/secretory products (ESPs) in its venom upon contact and during the parasitic infection process of insect hosts. A recurrent family of proteins found in this nematode’s venom is the CAP (cysteine-rich secretory protein/antigen 5/pathogenesis-related 1) protein, but the functional role of these proteins remains unknown. To elucidate the biological function, this study focused on characterising the secreted protein, first identified in the venom of the nematode’s parasitic stage, and the sequence retrieved from transcriptomic analysis. The structural comparisons of the Sc-CAP protein model, as determined by AlphaFold2, revealed related structures from other parasitic nematodes of vertebrates. Some of these closely related proteins are reported to have sterol-binding ability. The Sc-CAP recombinant protein was successfully produced in Escherichia coli in conjunction with a chaperone protein. The results showed that the Sc-CAP protein binds to cholesterol, and docking analyses of sterols on the protein revealed potential molecular interactions. Immunoassays performed in Galleria mellonella larvae revealed that this venom protein has an inhibitory effect against phenoloxidase and the antimicrobial response of insects. This suggests that the venom protein has an immunomodulatory function against insects, emphasising its importance during the parasite–host interaction. Full article

Background: Vitamin D is increasingly recognized not only for its role in skeletal development but also for its immunomodulatory and gastrointestinal effects. Maternal and neonatal vitamin D deficiency (VDD) has been associated with alterations in gut microbiota, impaired intestinal barrier integrity, and increased susceptibility to inflammatory conditions in neonates. However, the exact mechanisms linking perinatal vitamin D status to neonatal gastrointestinal morbidity remain incompletely understood. Methods: This review synthesizes current evidence (2015–2024) from clinical studies, animal models, and mechanistic research on the impact of VDD during pregnancy and the neonatal period on gastrointestinal health. Databases such as PubMed, Scopus, and Web of Science were systematically searched using keywords, including “vitamin D”, “neonate”, “gut microbiome”, “intestinal barrier”, and “necrotizing enterocolitis”. Results: Emerging data suggest that VDD in utero and postnatally correlates with dysbiosis, increased intestinal permeability, and elevated inflammatory responses in neonates. Notably, low 25(OH)D levels in mothers and newborns have been linked with a higher incidence of necrotizing enterocolitis (NEC), delayed gut maturation, and altered mucosal immunity. Vitamin D appears to modulate the expression of tight junction proteins, regulate antimicrobial peptides, and maintain microbial diversity through the vitamin D receptor (VDR). Conclusions: Understanding the gastrointestinal implications of early-life VDD opens a potential window for preventive strategies in neonatal care. Timely maternal supplementation and targeted neonatal interventions may mitigate gut-related morbidities and improve early-life health outcomes. Further longitudinal and interventional studies are warranted to clarify causality and optimal intervention timing. Full article

Chitosan and technical cashew nutshell liquid (CNSLt) have emerged as promising natural compounds due to their antimicrobial, immunomodulatory, and fermentation-modulating properties. This study aimed to evaluate the inclusion of chitosan and CNSLt as potential substitutes for the ionophore monensin on feed intake, ruminal fermentation, nitrogen balance, and microbial protein synthesis in steers. Five crossbred steers (Bos taurus), 18 months old with an average body weight of approximately 350 kg and fitted with permanent ruminal cannulas, were assigned to a 5 × 5 Latin square design. The experimental diets consisted of: (1) control (CON), (2) monensin (MON; 25 mg/kg of dry matter [DM]), (3) chitosan (CHI; ≥850 g/kg deacetylation degree, 375 mg/kg DM), (4) CNSLt (500 mg/kg DM), and (5) CNSLt + CHI (500 + 375 mg/kg DM). Supplementation with CHI or CNSLt + CHI reduced the intake of dry matter, crude protein, and neutral detergent fiber. Additionally, fecal excretion of whole corn kernels increased in these treatments. Ruminal fermentation parameters were affected, with the CNSLt + CHI treatment promoting higher molar proportions of propionate and acetate, along with reduced estimated methane emissions. However, purine derivatives, microbial protein synthesis, and nitrogen balance were not significantly affected by any of the treatments. These results suggest that CNSLt and CHI, particularly when combined, may serve as effective natural alternatives to monensin in high-grain diets for ruminants. Full article

Donkey milk has received increasing attention in recent years due to its unique nutritional composition and potential biological activities. This comprehensive review analyzed the main nutritional components of donkey milk, including proteins, lipids, carbohydrates, vitamins, and minerals, while also examining its significant biological activities such as antioxidant, antimicrobial, immunomodulatory, and anti-inflammatory properties. The protein profile of donkey milk is notable for its high proportion of whey proteins (55–65%), resembling human milk more closely than cow milk. Its relatively low-fat content (approximately 1.29%) with higher proportions of unsaturated fatty acids provides nutritional advantages for specific dietary needs. The carbohydrate content, primarily lactose, contributes to energy provision and calcium absorption. Donkey milk is also distinguished by its rich vitamin profile, particularly vitamin C (about 4.75 times higher than cow milk), and essential minerals including calcium, phosphorus, and zinc. The biological activities of donkey milk extend to various applications in infant nutrition, particularly for children with cow milk protein allergies, potential medical treatments for infections and inflammatory conditions, and cosmetic formulations. Despite these promising attributes, the donkey milk industry faces challenges including low milk yield, lack of standardized production methods, and quality control measures. The sustainable development of the donkey milk industry requires comprehensive approaches to resource protection, technological innovation, brand building, and supportive policies to realize its full potential in contributing to human health and economic development. Full article

Propolis is a natural resinous substance produced by honeybees that has many biological activities. For thousands of years, it has been widely used as a dietary supplement and traditional medicine to treat a variety of ailments due to its antimicrobial, anti-inflammatory, antioxidant, immunomodulatory, and wound-healing properties. Nutritional supplements and foods may interact with drugs both pharmacodynamically and pharmacokinetically, which could raise clinical concerns. Background/Objectives: This study aimed to investigate the effect of propolis on the plasma disposition of enrofloxacin and to assess the potential pharmacokinetic interaction in rabbits. Methods: In this study, enrofloxacin was applied per os (20 mg/kg) and IM (10 mg/kg) and with propolis (100 mg resin/kg) administration in four groups of rabbits (each of six individuals). Heparinized blood samples were collected at 0, 0.1, 0.3, 0.5, 1, 2, 4, 8, 12, and 24 h post-administration. HPLC-FL was used to analyze the plasma concentrations of enrofloxacin and its active metabolite ciprofloxacin following liquid–liquid phase extraction, i.e., protein precipitation with acetonitrile and partitioning with sodium sulfate. Results: The results revealed that propolis coadministration significantly affected the plasma disposition of enrofloxacin and its active metabolite after both per os and intramuscular administration routes. Significantly greater AUC (48.91 ± 11.53 vs. 26.11 ± 12.44 µg.h/mL), as well as longer T_1/2λz (11.75 ± 3.20 vs. 5.93 ± 2.51 h) and MRT (17.26 ± 4.55 vs. 8.96 ± 3.82 h) values of enrofloxacin and its metabolite ciprofloxacin, were observed after the coadministration of propolis compared to enrofloxacin alone following both per os and IM routes in rabbits. Conclusions: The concurrent use of propolis and prescription medications may prolong the half-life (T_1/2λz) and increase the systemic availability of chronically used drugs with narrow therapeutic indices. The repeated use of drugs such as antibiotics, heart medications, and antidepressants, or drugs with a narrow therapeutic index such as antineoplastic and anticoagulant agents, can cause toxic effects by raising blood plasma levels. Considering the varied metabolism of rabbits and humans, further validation of this study may require thorough clinical trials in humans. Full article

The gut serves as the main site for nutrient digestion and absorption. Simultaneously, it functions as the body’s largest immune organ, playing a dual role in sustaining physiological equilibrium and offering immunological defense against intestinal ailments. Maintaining the structural and functional integrity of the intestine is paramount for ensuring animal health and productivity. Puerarin, a naturally derived isoflavonoid from the Pueraria species, exhibits multifaceted bioactivities, such as antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. Emerging evidence highlights puerarin’s capacity to enhance gut health in farm animals through four pivotal mechanisms: (1) optimization of intestinal morphology via crypt-villus architecture remodeling, (2) augmentation of systemic and mucosal antioxidant defenses through Nrf2/ARE pathway activation, and (3) reinforcement of intestinal barrier function by regulating tight junction proteins (e.g., ZO-1, occludin), mucin secretion, intestinal mucosal immune barrier, the composition of microbiota, and the derived beneficial metabolites; (4) regulating the function of the intestinal nervous system via reshaping the distribution of intestinal neurons and neurotransmitter secretion function. This review synthesizes current knowledge on puerarin’s protective effects on intestinal physiology in farm animals, systematically elucidates its underlying molecular targets (including TLR4/NF-κB, MAPK, and PI3K/Akt signaling pathways), and critically evaluates its translational potential in mitigating enteric disorders such as post-weaning diarrhea and inflammatory bowel disease in agricultural practices. Full article

Honey and other bee products, including propolis, royal jelly, and bee pollen, are widely recognized for their medicinal properties. Among their numerous biological activities, their anti-inflammatory and immunomodulatory effects have gained significant attention in recent years. Immune and inflammatory disorders contribute significantly to the development of chronic conditions, including cancer and diabetes. Bee-derived products, along with their bioactive compounds such as polyphenols, have shown promising therapeutic effects in modulating inflammatory mediators. Studies indicate that these products help regulate tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), and interleukin-7 (IL-7) levels while reducing reactive oxygen species (ROS) production. Additionally, both in vitro and in vivo research, along with clinical studies, highlight their role in enhancing immune responses by activating B and T lymphocytes. This review explores the molecular mechanisms underlying these properties, emphasizing the role of bioactive compounds such as flavonoids, phenolic acids, and proteins in modulating immune responses and reducing inflammation. Evidence from in vitro, in vivo, and clinical studies suggests that honey and bee products influence cytokine production, regulate immune cell activity, and mitigate oxidative stress, making them potential therapeutic agents for inflammatory and immune-related disorders. To gather relevant information, databases such as Google Scholar, PubMed, and ScienceDirect were searched using various keyword combinations, including immunomodulatory, anti-inflammatory, bee products, honey, propolis, royal jelly, bee venom, and bee pollen. Given their anti-inflammatory, immune-protective, antioxidant, anti-apoptotic, and antimicrobial properties, bee products remain a subject of interest for further clinical evaluation. Full article

This study aimed to evaluate whether the addition of a phytobiotic additive formulated based on cinnamon and oregano essential oils (50% free and 50% microencapsulated) combined with turmeric extract and tannins to the diet of cows has beneficial effects on health, productivity, and milk quality. In a completely randomized design, eighteen Jersey cows were used in a compost barn system over 45 days. The cows were divided into two homogeneous groups: one control (without additive; n = 9) and another treatment (with a phytobiotic at a dose of 2 g/cow/day; n = 9). The diet was formulated based on corn silage, hay and concentrate for daily 30 L/cow production. Blood and milk samples were collected at 15-day intervals. There was a treatment × day interaction: cows that consumed the phytobiotic additive produced a more significant amount of milk at days 14, 17, 18, 30, 39 and 45 (p ≤ 0.05). When we corrected milk production for fat percentage, we observed higher milk production in the cows that consumed phytobiotics compared to the control during the experimental period (p = 0.01). The feed intake of cows fed phytobiotics was lower (p = 0.01). Thus, feed efficiency was better in cows that consumed phytogenics. There was a higher percentage of fat in the milk of cows that consumed phytobiotics and a higher amount of polyunsaturated fatty acids compared to the control (p = 0.02). There was an increase in total protein and globulin levels (p = 0.01), which may be associated with the interaction of the antimicrobial, antioxidant, and immunomodulatory properties of the phytobiotic additive. An increase in immunoglobulins (p = 0.01) and a reduction in acute-phase proteins (p ≤ 0.05) were observed in the blood of cows in the phytobiotic group. Lower levels of TNF-α, IL-1β and IL-6 and higher levels of IL-10 in the serum of cows that consumed the phytoactive (p = 0.01) reaffirm the anti-inflammatory effect of the additive. Lower levels of lipid peroxidation (TBARS) and reactive oxygen species (ROS) were observed in the serum of cows in the phytobiotic group. Greater catalase and superoxide dismutase activity was observed in cows that consumed the phytogenic (p < 0.01). Therefore, it can be concluded that the additive in question has antioxidant, immunological, and anti-inflammatory actions and has the potential to improve productive performance when corrected for milk fat. Full article

The whey protein (WP) fraction represents 18–20% of the total milk nitrogen content. It was originally considered a dairy industry waste, but upon its chemical characterization, it was found to be a precious source of bioactive components, growing in popularity as nutritional and functional food ingredients. This has generated a remarkable increase in interest in applications in the different sectors of nutrition, food industry, and pharmaceutics. WPs comprise immunoglobulins and proteins rich in branched and essential amino acids, and peptides endowed with several biological activities (antimicrobial, antihypertensive, antithrombotic, anticancer, antioxidant, opioid, immunomodulatory, and gut microbiota regulation) and technological properties (gelling, water binding, emulsification, and foaming ability). Currently, various process technologies and biotechnological methods are available to recover WPs and convert them into BioActive Peptides (BAPs) for commercial use. Additionally, in silico approaches could have a significant impact on the development of novel foods and/or ingredients and therapeutic agents. This review provides an overview of current and emerging methods for the production, selection, and application of whey peptides, offering insights into bioactivity profiling and potential therapeutic targets. Recent updates in legislation related to commercialized WPs-based products are also presented. Full article

Mycobacterium indicus pranii (MIP), an atypical mycobacterium originally developed as an anti-leprosy vaccine, has emerged as a potent immunomodulator with diverse therapeutic applications. Despite its clinical significance, molecular mechanisms underlying MIP’s immunomodulatory properties remain largely unexplored. Bacterial phosphatases are recognized as crucial virulence factors that enable pathogens to evade host defenses by modulating host immune signaling pathways, including phosphoinositide metabolism. MIP_07528 was identified as a putative protein tyrosine phosphatase B (PtpB) ortholog through in silico analysis, with significant sequence conservation observed within catalytic domains of pathogenic mycobacterial PtpB proteins. Phosphatase activity was detected in both cell lysate and culture filtrate fractions, revealing differential expression patterns between MIP and M. tuberculosis. Upregulation of MIP_07528 was demonstrated under oxidative stress, suggesting involvement in stress adaptation. The recombinant protein exhibited distinctive kinetic properties, characterized by higher substrate affinity yet increased susceptibility to oxidative inactivation compared to its M. tuberculosis counterpart. In macrophages, MIP_07528 suppressed pro-inflammatory cytokines while enhancing anti-inflammatory IL-10 production. These findings establish MIP_07528 as a functional phosphatase that may contribute to MIP’s immunomodulatory properties. This work advances understanding of phosphatase function in non-pathogenic mycobacteria while providing insights into virulence factor evolution and establishing a foundation for novel antimicrobial strategies. Full article

Hemocyanins are oxygen-transporting proteins found in crustaceans and other arthropods, playing key roles in immune defense and metabolic regulation. Due to their stability and bioactive properties, Hcs have gained increasing interest in biotechnological and biomedical applications. However, detailed biophysical characterization is crucial to understanding their functional potential. In this study, the hemocyanin was extracted and purified from Macrobrachium acanthurus (HcMac) using ultracentrifugation and size-exclusion chromatography. The molecular mass of HcMac was determined by SDS-PAGE electrophoresis, MALDI-TOF mass spectrometry, and analytical ultracentrifugation. Spectroscopic analyses, including UV-Vis absorption, fluorescence emission, and light scattering intensity, were used to assess the structural stability of the compound under various pH conditions. HcMac was identified as a hexameric protein (~450 kDa) composed of monomeric subunits of 75 and 76 kDa. The protein maintained its oligomeric stability and oxygen-binding affinity in the pH range of 5.0–7.4. However, extreme pH conditions (below 4.4 and above 7.5) induced structural alterations, leading to dissociation and conformational changes, as evidenced by fluorescence emission and UV-Vis spectra. The isoelectric point was determined to be between pH 4.3 and 5.3, consistent with other crustacean HCs. These findings reinforce the structural robustness of HcMac and suggest its potential for biotechnological applications. The high stability of HcMac under physiological pH conditions indicates its suitability for biomedical research, including immunomodulatory and antimicrobial applications. Future studies integrating bioinformatics, proteomics, and immunological assays will be essential to explore the therapeutic potential of HcMac. Full article

Scolopendra subspinipes, commonly known as the Chinese red-headed centipede, has been utilized in traditional East Asian medicine for centuries to treat conditions such as chronic pain, inflammation, convulsions, and infections. Recent pharmacological investigations have uncovered a wide array of bioactive molecules—including peptides, alkaloids, and polysaccharide–protein complexes—from both venom and whole-body extracts. This review synthesizes findings from 45 in vitro, in vivo, and clinical studies investigating the pharmacological effects of venom-derived and whole-body-derived compounds from S. subspinipes across multiple domains, including analgesic, anti-inflammatory, antimicrobial, antifungal, antioxidant, antitumor, antithrombotic, anti-fibrotic, and neuroprotective activities, along with a brief scoping review of clinical practice guidelines. Key venom-derived compounds such as the peptide SsmTX-I, immunomodulatory antimicrobial peptide scolopendrasin IX, and antitumor peptide scolopentide exhibit strong mechanistic rationale and preclinical efficacy, positioning them as lead candidates for clinical development. Compounds derived from whole-body extracts, including alkaloids and polysaccharide–protein complexes, also demonstrate promising therapeutic potential. Mechanistic studies suggest these compounds operate via distinct pathways—such as ion-channel inhibition, NF-κB suppression, and apoptosis induction—offering potential advantages over existing therapies. However, current evidence remains primarily preclinical, and challenges such as extract variability, immunogenicity, and lack of standardized dosing must be addressed. Future research should prioritize isolation and structural optimization of key peptides, standardized formulation development, toxicological profiling, and early-phase human trials. The integration of traditional knowledge and modern pharmacological insights underscores the potential of venom- and whole-body-derived S. subspinipes agents to enrich the drug discovery, particularly for conditions with unmet therapeutic needs. Full article