Search Results (460)

Fermented milk is rich in probiotics, peptides, vitamins, and minerals, which are used as routine food supplements and are of great benefit for regulating human health. This study explored the mechanism of Lactobacillus delbrueckii ssp. bulgaricus CGMCC 21287 or Lacticaseibacillus casei CGMCC 15956 fermented milk for alleviating acute alcoholic liver injury. We found that fermented milk was associated with reduced activation of TLR4/NF-κB pathways, alleviating alcohol-induced liver inflammation. Meanwhile, the two probiotics regulated different intestinal microbial communities in mice. The LC group specifically increased the abundance of probiotics such as Roseburia, unidentified_Lachnospiraceae, and Allobaculum, and decreased the abundance of pathogenic bacteria such as Enterococcus and Shigella. The LB group increased the abundance of Adlercreutzia and Ruminococcus, thereby increasing butyric acid, acetic acid, and valeric acid levels and decreasing lipopolysaccharide (LPS) production. These results suggest that daily intake of fermented milk can attenuate alcohol-induced acute liver injury in mice via the gut–liver axis, though differences exist in the mechanisms of action and areas of emphasis. Full article

Liquid infant formula has garnered increasing attention due to its mild thermal processing and superior retention of bioactive nutrients. Within such matrices, the lipid source is a critical determinant of protein digestion behavior, yet its influence on peptide bioavailability and intestinal homeostasis remains undefined. Given that efficient peptide absorption is vital for the systemic delivery of bioactivity in infants, understanding the lipid–protein synergy is essential for formula optimization. Moreover, excessive oxidative stress is closely associated with impaired intestinal health and developmental disorders in infants, making the regulation of oxidative stress crucial for maintaining intestinal function. The present study evaluated the effects of three distinct lipid sources—soybean oil (SM), bovine milk fat (BM), and goat milk fat (GM)—on the physicochemical stability, proteolytic digestion, peptide release, intestinal absorption, and oxidative stress modulation of goat-milk-based infant formula. An integrated approach combining physicochemical characterization, in vitro simulated infant digestion, and a Caco-2 intestinal epithelial cell model was employed. we demonstrate that all three lipids (3% w/w) formed stable emulsions with uniform spherical structures and mean particle diameters of 117–300 nm, as visualized by laser confocal microscopy. Following in vitro simulation of infant gastrointestinal digestion, the SM group exhibited the most extensive protein hydrolysis, yielding the highest total peptide content (4.28 ± 0.10 mg/mL) and generated the highest number of peptides identified by LC-MS/MS (474 types). Bioinformatic analysis predicted that peptides from all groups possess potential antihypertensive, hypoglycemic, and immunomodulatory activities. The Caco-2 monolayer cell model demonstrated that although the GM group produced fewer identified peptide species than the SM group (365 types), it achieved significantly higher intestinal peptide absorption rate (55.34 ± 1.05%). Furthermore, the GM digests provided superior protection against H₂O₂-induced oxidative stress in Caco-2 cells, markedly reducing reactive oxygen species levels and suppressing the expression of pro-inflammatory cytokines TNF-α and IL-6. Collectively, these findings reveal that while soybean oil promotes more extensive proteolysis, the use of homologous goat milk lipid enhances peptide bioaccessibility and confers potential cytoprotective effects on intestinal epithelial cells, underscoring its potential as a preferred lipid source in infant formula formulations. Full article

Insulin resistance is a multifactorial cellular state involving coordinated alterations in protein homeostasis and organelle function; however, its proteome-wide organization and response to bioactive peptides remain incompletely defined. In this study, we employed DIA-based quantitative proteomics to characterize global protein abundance changes associated with insulin resistance in HepG2 cells and to examine proteomic remodeling following treatment with a camel milk-derived peptide (P2). Comparative proteomic profiling revealed that insulin-resistant cells exhibit extensive reorganization of protein networks linked to redox regulation, endoplasmic reticulum protein processing, mitochondrial metabolism, lysosomal function, and extracellular matrix-associated components. Gene Ontology, KEGG pathway, protein domain, and subcellular localization enrichment analyses consistently indicated disruption of organelle-associated proteomic architecture rather than isolated pathway perturbations. Peptide TYYPPQ treatment was associated with selective, rather than global, proteomic shifts, prominently affecting mitochondrial and peroxisome-associated protein groups as well as extracellular and secretory proteins. Enrichment and localization analyses suggest that peptide exposure reshapes organelle-linked protein representation patterns without implying direct activation of signaling pathways or physiological restoration. Collectively, these results define insulin resistance and peptide responsiveness at a systems-level proteomic resolution and establish an organelle-resolved framework for interpreting peptide-induced proteomic remodeling in insulin-resistant hepatocyte models. This dataset provides a foundation for future targeted functional validation of candidate pathways identified through proteomic association. Full article

Gut ischemia/reperfusion (I/R) injury releases damage-associated molecular patterns (DAMPs), such as extracellular cold-inducible RNA-binding protein (eCIRP). Milk fat globule–epidermal growth factor VIII-derived oligopeptide 3 (MOP3) is a novel peptide enabling macrophage uptake of eCIRP via αvβ3-integrin. MOP3 reduces inflammation in gut I/R, but its mechanisms are not completely understood. We hypothesized MOP3 promotes macrophage polarization toward an anti-inflammatory, M2-like phenotype in gut I/R. We induced gut I/R in mice through 60 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Intestines were evaluated for macrophage polarization by flow cytometry and immunofluorescence histology. Peritoneal cavity macrophages were isolated from mice and treated with eCIRP, MOP3, α_vβ₃-antibody, and/or naïve IgG for 4 or 24 h. Polarity was assessed by flow cytometry, qPCR, and ELISA. Compared to the sham, the M2 proportion after gut I/R decreased by 22.7%, and the M1 proportion increased by 241%. MOP3 treatment increased the M2 proportion by 64.3%, and the M1 proportion decreased by 22.7%. In eCIRP-stimulated macrophages, MOP3 treatment increased M2-like and reduced M1-like cell-surface markers, gene expression, and cytokine levels. α_vβ₃ antibody dramatically reduced MOP3′s effects. MOP3 promotes M2 polarization through α_vβ₃ integrin-mediated clearance of eCIRP, a novel mechanism whereby MOP3 reduces gut I/R injury. Full article

Buffaloes are vital livestock in South-East Asia, attributed to their adaptation to hot and humid climates as well as their capacity to produce high-quality milk and meat. However, the texture of buffalo meat is suboptimal and its slow growth rate restricts the development of the buffalo farming industry. Consequently, studies exploring the key biochemical factors associated with buffalo muscle development have become a research focus. CircRNAs are a class of non-coding RNAs which can function as molecular sponges, participate in protein scaffold formation, and encode short peptides. Previous studies have shown that circRNAs are capable of regulating muscle development; however, relatively few reports have addressed their association with buffalo muscle development. In this study, data from Western blotting and RT-qPCR showed that circCOPS8 significantly enhanced the differentiation of buffalo myoblasts while inhibiting their proliferation (p < 0.05). In contrast, in a mouse model of muscular injury, circCOPS8 prevented the repair of injured muscles. Additionally, RIP-qPCR assays confirmed that circCOPS8 could bind to IGF2BP3 (p < 0.05). Furthermore RT-qPCR and transcriptome sequencing results revealed that circCOPS8 inhibited cell growth by upregulating the expression of genes such as ATR (p < 0.05). Our findings suggested that circCOPS8 promoted the differentiation and apoptosis of buffalo myoblasts while inhibiting their proliferation. The inhibition of cell proliferation was primarily mediated by the binding of circCOPS8 to IGF2BP3 and the promotion of ATR gene expression. This study investigated the role and underlying mechanism of circCOPS8 in buffalo myoblasts, which will extend our understanding of non-coding RNA-mediated regulation of buffalo muscle development, with the ultimate goal of improving the meat quality of buffaloes. Full article

Background/Objectives: Hand, foot, and mouth disease (HFMD) is a major public health concern primarily caused by human enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), coxsackievirus A6 (CVA6), and certain coxsackievirus B serotypes. Currently available EV-A71 vaccines lack cross-protective efficacy against other serotypes, highlighting the urgent need for multivalent and broadly effective enterovirus vaccines. Methods: Immunoinformatics approaches were used to predict highly immunogenic B-cell and T-cell epitopes, which were assembled to construct a novel multivalent epitope vaccine, rCV-A3V, followed by in silico validation. Recombinant protein expression was confirmed by Western blotting and immunofluorescence assays. The immunogenicity was evaluated in Balb/c mice following intranasal immunization. Results: A preliminary safety evaluation demonstrated that the rCV-A3V vaccine was well tolerated in the mouse model, with no abnormal changes in body weight observed after immunization. In addition, the target protein was successfully expressed. Intranasal immunization induced a strong Th1-biased immune response, robust serum neutralizing and IgG antibody responses, and pronounced mucosal immunity, including elevated sIgA and IgG levels in nasal lavage fluid, sIgA in feces, and substantial sIgA responses in milk. Dominant epitope peptides were also identified. Conclusions: The intranasal live attenuated rCV-A3V vaccine successfully induced humoral, mucosal, and cellular immune responses against EV-A71, CVA16, CVA6, and CVB3, demonstrating broad immunogenicity. These findings provide experimental evidence supporting its potential as a candidate vaccine for HFMD. Full article

Lactiplantibacillus plantarum EL2, isolated from traditional fermented yak milk in the high-altitude Gannan Tibetan Autonomous Prefecture, produces the class IIb bacteriocin PlnJK. This study established three distinct cultivation models that critically influenced bacteriocin yield. Microbial co-culture was found to enhance the stress tolerance of EL2, significantly boosting PlnJK production. The optimal inducing strain, Enterococcus faecalis MH2, increased the bacteriocin inhibition zone diameter from 15.38 mm to 25.58 mm. Following optimization of key parameters—initial inoculum concentration (10⁷ CFU/mL), inoculation ratio (3:1, EL2:MH2), and initial pH (6.0)—the inhibition zone diameter reached 30.32 mm, representing a 1.97-fold increase over pure culture. Co-culture not only advanced the onset but also extended the duration of bacteriocin synthesis. Throughout the 24 h incubation, cell density, AI-2 autoinducer concentration, and the expression of key regulatory genes were significantly elevated in co-culture compared to monoculture, aligning with a cell-density-dependent, quorum-sensing (QS) regulatory paradigm. Bacteriocin production was co-regulated by two QS pathways: the AI-2/luxS system and the plnA-mediated autoinducing peptide (AIP). Gene expression analysis revealed differential temporal regulation: luxS expression was higher during the exponential phase (2.29 vs. 1.42 in stationary phase), while plnA exhibited the opposite pattern (1.42 in exponential vs. 2.21 in stationary phase). This indicates that the AI-2/luxS pathway drives strong induction during active growth, whereas plnA/AIP-mediated promotion becomes predominant later. The stationary-phase effect is likely triggered by the accumulation of specific MH2 metabolites, which impose an environmental stress on EL2, stimulating the pln-encoded regulatory system and further enhancing bacteriocin yield. This work provides an economically viable strategy and a novel theoretical framework for optimizing microbial cultivation, enhancing bacteriocin production, and elucidating the complex QS-mediated regulatory mechanisms involved. Full article

Widespread, sometimes careless use of antibiotics has accelerated the rise and spread of antibiotic-resistant pathogens. These resistant bacteria are now often found in animal-based foods like meat, milk, and eggs, as well as in plant-based foods such as fruits and vegetables. Contaminated food is a key way these bacteria travel through the food chain and eventually reach people. This review brings together global trends in antibiotic contamination, explains the molecular mechanisms underlying antimicrobial resistance, and examines current approaches to addressing this problem. It also highlights new technologies that could work alongside or improve on traditional antibiotics. Some promising options are antimicrobial peptides, natural bioactive compounds, nanomaterials, and monoclonal antibody-based therapies. Tackling antimicrobial resistance requires teamwork across fields such as microbiology, food science, pharmacology, environmental science, and public health. Future research should strengthen global surveillance, standardize resistance-assessment methods, expand studies on non-bacterial pathogens, and ensure rigorous evaluation of novel therapies for pharmacokinetics, toxicity, scalability, and regulatory compliance. Ongoing global cooperation and new scientific ideas are crucial to slow the spread of resistant microbes and protect food safety and human health. Full article

Lactoferrin (Lf) and Lf-derived peptides are multifunctional milk components with potential applications in food preservation due to their antibacterial and antioxidant properties. In this study, the antibacterial and antioxidant activities of bovine lactoferrin and Lf-derived peptides obtained by enzymatic hydrolysis with pepsin, trypsin, and chymotrypsin were evaluated. Antibacterial activity was assessed against four foodborne pathogens and spoilage microorganisms (Escherichia coli, Listeria monocytogenes, Staphylococcus epidermidis, and Latilactobacillus sakei), while antioxidant activity was determined using four complementary assays. Lf showed stronger antibacterial activity than the corresponding hydrolysates against all tested strains, while the hydrolysates notably inhibited Listeria monocytogenes and Latilactobacillus sakei. Both Lf and its peptides showed lower antioxidant capacity than Trolox, although native Lf and its peptides markedly inhibited lipid peroxidation. Lf peptides demonstrated greater antioxidant activity in the superoxide scavenging and FRAP assays. Low-molecular-weight peptides (<10 kDa) contributed most to antioxidant activity, while mass spectrometry analysis revealed peptide sequences rich in hydrophobic and electron-donating amino acid residues, providing mechanistic insight into the observed activities. Overall, these findings highlight the potential of lactoferrin and its enzymatic hydrolysates as natural antimicrobial and antioxidant agents for food preservation. Full article

Background: Antimicrobial resistance (AMR) is a global healthcare threat. Traditional largely non-selective antibiotics produce side effects due to the natural host microbiome being modified creating a loss in homeostasis. In women, AMR is a cause of acute generational impact. For example, bacterial vaginosis (BV), the most common gynecological infection in reproductive-age women, is a serious public health concern due to its high rates of recurrence, secondary infections, and reproductive issues; and two currently prescribed antibiotics for BV do not fully resolve the symptoms. Objective: The strong need for innovative, potent, safe, and selective therapeutics has prompted a search for such bioactive molecules in milk. Resulting from 200 million years of evolutionary pressure, mammalian lactation not only nourishes infants, but it has also been under relentless Darwinian selective pressure to provide protection from a variety of infections. Methods: Computationally designed human-milk-inspired peptides (AMPs) were tested in standard microbicidal assays for activity against BV pathogens, and evaluated for stability and safety. Results: Several AMPs are bactericidal towards Gardnerella vaginalis, a major BV-associated pathogen, and other BV-associated pathogens. Some novel AMPs do not impact the viability of key lactobacilli linked to a healthy vaginal microbiome. These stable, membrane-acting cationic AMPs reduce inflammation during an infection assay and are safe in EpiVag organoid tissues. Conclusions: AMPs can address concerns like non-selectivity and antibiotic resistance—thereby addressing AMR. Lead AMPs from this study offer a promising solution for the development of novel therapeutics for the treatment of BV, which may reduce the burden of AMR. Full article

Goat reproductive performance is a key determinant of the productivity and economic value of goat farming, especially in meat and milk production. In a previous study, to investigate the genetic basis of prolificacy, we divided goats into groups according to their consistent reproductive performance (producing either single kids or twins) over five consecutive kidding cycles, and performed whole-genome resequencing and RNA-seq analysis on their ovarian tissues. Through integrated analysis, we identified three candidate genes—IGF2BP1 (insulin-like growth factor 2 mRNA-binding protein 1), CDC25A (cell division cycle 25A), and RXFP2 (relaxin family peptide receptor 2)—as potential key regulators of reproductive capacity. Using goat ovarian granulosa cells, we systematically assessed the impact of each gene through gain- and loss-of-function experiments. Overexpression of IGF2BP1 promoted cell proliferation and suppressed apoptosis, underscoring its role in maintaining cellular viability. Conversely, its knockdown significantly impeded growth and induced cell death. Similarly, CDC25A enhanced granulosa cell proliferation, whereas its knockdown led to marked growth impairment and increased apoptosis. Proliferation was also enhanced by RXFP2 overexpression but impaired upon its knockdown, suggesting that RXFP2 is functionally important for follicular development. Collectively, these findings establish IGF2BP1, CDC25A, and RXFP2 as fundamental regulators of granulosa cell dynamics and ovarian follicular development, providing crucial functional insights and promising targets for genetic selection to enhance reproductive efficiency in goats. Full article

Moroccan lben is a traditional spontaneously fermented milk widely consumed across the Maghreb. In this review, we synthesize data on spontaneously fermented milks from Morocco and the wider Maghreb–Middle Eastern region to infer the likely microbiota of Moroccan lben, with particular emphasis on dominant lactic acid bacteria such as Lactococcus lactis, Streptococcus thermophilus, Leuconostoc mesenteroides and lactobacilli sensu lato, alongside yeasts including Kluyveromyces marxianus and Saccharomyces cerevisiae. These communities drive a staged fermentation in which early mesophilic lactic acid bacteria (LAB) rapidly acidify the milk and initiate coagulation, intermediate heterofermentative LAB and yeasts generate key aroma compounds and mild effervescence, and late acid-tolerant lactobacilli contribute to flavor refinement and microbiological stability. We summarize how these bacteria and fungi collectively shape physicochemical, sensory and safety attributes through pH reduction, organic acid and bacteriocin production, proteolysis, and volatile formation, and discuss potential nutritional and health-related effects associated with bioactive peptides and putative probiotic strains. Finally, we identify major research gaps, including the need for high-resolution, culture-dependent and culture-independent studies, systematic safety assessments, and rational design of starter and adjunct cultures that reproduce traditional sensory profiles while improving process control. Full article

Cheese whey, a low-value by-product of cheese production, has gained renewed attention within the transition toward sustainable and circular food systems. Despite posing environmental challenges due to its high biochemical and chemical oxygen demand, whey retains a substantial proportion of milk nutrients, notably high-quality proteins that can be converted into bioactive peptides with potential health benefits. These peptides have been shown to modulate key biological pathways, including angiotensin-converting enzyme inhibition, nitric oxide bioavailability, oxidative stress balance, and inflammatory signaling, providing mechanistic plausibility for cardioprotective and immunomodulatory effects. However, the translation of promising in vitro and animal findings into consistent human health outcomes remains constrained by variability in peptide composition, processing conditions, bioavailability, and study design. This narrative review critically synthesizes current evidence on the functional properties of whey-derived peptides, with particular emphasis on cardiovascular and immunomodulatory outcomes across experimental models. In addition, the review situates whey upcycling within the Portuguese agro-food context, highlighting regional cheese production as both an environmental challenge and an opportunity for sustainable innovation. By integrating mechanistic evidence with sustainability-driven valorization strategies, this review aims to clarify the translational potential of whey-derived peptides as functional food ingredients. Full article

Hypertension is a major controllable risk factor associated with cardiovascular disease, myocardial infarction, stroke, heart failure, and end-stage diabetes. While commercial antihypertensive drugs are effective in managing high blood pressure, they often come with a range of side effects. Additionally, individuals who begin anti-hypertensive treatment may need to continue these medications throughout their lifetime. In response to these challenges, recent studies have focused on the potential of antihypertensive peptides and hydrolysates derived from food proteins. Food protein-derived peptides and hydrolysates help lower blood pressure (hypertension) primarily by inhibiting the renin–angiotensin system (RAS). Some peptides or protein hydrolysates derived from milk and fish have been proven to be safe and effective anti-hypertensive products, and they are currently on the market. The bioactive peptides and hydrolysates derived from plant proteins with a long history of safe consumption are generally considered safe and have shown some advantages over animal protein-derived peptides. This review provides an up-to-date overview of plant protein-derived antihypertensive peptides and hydrolysates, covering their ACE- and renin-inhibiting activities and mechanisms, in vivo and clinical evidence, bioavailability, production and commercialization challenges, and perspectives for future research. Full article

Pseudomonas aeruginosa elastase LasB accelerates refrigerated food spoilage through proteolytic degradation of muscle and milk proteins. While Marrubium vulgare essential oil terpenes exhibit antimicrobial activity, their weak potency and nonspecificity limit direct food preservation applications. This computational study aimed to rationally redesign terpene scaffolds into predicted selective LasB inhibitors. A virtual library of 635 terpene–peptide–phosphinic acid hybrids (expanded to 3940 conformers) was evaluated using consensus molecular docking (Glide/Flare) against LasB (PDB: 3DBK) and three human off-target proteases. Top candidates underwent duplicate 150 ns molecular dynamics simulations with MM/GBSA binding free-energy calculations. Computational screening identified thymol–Leu–Trp–phosphinic acid as the lead candidate with predicted binding affinity of −12.12 kcal/mol, comparable to reference inhibitor phosphoramidon (−11.87 kcal/mol), and predicted selectivity index of +0.12 kcal/mol representing a 2.3 kcal/mol advantage over human proteases. Molecular dynamics simulations indicated exceptional stability (98.7% stable frames, 0.12 Å inter-replica RMSD) with consistent zinc coordination. Structure–activity analysis revealed phosphinic zinc-binding groups (+1.57 kcal/mol), Leu–Trp linkers (+2.47 kcal/mol), and phenolic scaffolds (+1.35 kcal/mol) as predicted optimal structural features. This in silico study provides a computational framework and prioritized candidate set for developing natural product-derived food preservatives. All findings represent computational predictions requiring experimental validation through enzymatic assays, food model studies, and toxicological evaluation. Full article