Search Results (2,545)

Colostrum is a nutrient-rich fluid secreted by mammals shortly after birth, primarily to provide passive immunity and support early immune development in newborns. Among its various sources, bovine colostrum is the most widely used supplement due to its high bioavailability, safety profile, and clinically supported health benefits. Rich in immunoglobulins, lactoferrin, growth factors, and antimicrobial peptides, bovine colostrum exhibits diverse biological activities that extend beyond neonatal health. Recently, the rising prevalence of cancer—driven by environmental stressors such as radiation, processed foods, and chronic inflammation, as well as non-environmental hereditary factors including germline mutations, family history, and epigenetic inheritance—has fueled interest in natural adjunctive therapies. Scientific studies have explored the anticancer potential of bovine colostrum, highlighting its ability to modulate immune responses, inhibit tumor growth, induce apoptosis in cancer cells, and reduce inflammation. Key components including lactoferrin and proline-rich peptides have been identified as contributors to these effects. Additionally, bovine colostrum may help reduce the side effects of standard cancer treatments, such as mouth sores from chemotherapy or weakened immune systems, by helping to heal tissues and boost the body’s defenses. While large-scale clinical studies are still needed, current findings suggest that bovine colostrum holds promise as a supportive element in integrative cancer care. In conclusion, bovine colostrum represents a safe, bioactive-rich natural supplement with multifaceted therapeutic potential, particularly in oncology, owing to its key components such as lactoferrin, immunoglobulins, growth factors (e.g., IGF-1, TGF-β), and proline-rich polypeptides (PRPs), which contribute to its immunomodulatory, anti-inflammatory, and potential anticancer effects. Ongoing and future research will be crucial to fully understand its mechanisms of action and establish its role in evidence-based cancer prevention and treatment strategies. Full article

Phycobiliproteins have gained increasing attention for their antidiabetic potential, yet the specific bioactive peptides and their targets and molecular mechanisms have remained unclear. In this study, four peptides with potential hypoglycemic activity were identified through virtual screening. Network pharmacology was employed to elucidate their hypoglycemic mechanism in the treatment of T2DM. A subsequent in vitro assay confirmed that the synthesized peptides, GR-5, SA-6, VF-6, and IR-7, exhibited significant inhibitory activity against α-glucosidase and DPP-IV. In insulin-resistant HepG2 models, all four peptides exhibited no cytotoxicity. Among them, GR-5 demonstrated the most promising therapeutic potential by remarkably enhancing cellular glucose consumption capacity. Furthermore, GR-5 administration substantially increased glycogen synthesis and enzymatic activities of hexokinase and pyruvate kinase with statistically significant improvements compared to the control groups. This study provides novel peptide candidates for T2DM treatment and validates an integrative strategy for targeted bioactive peptide discovery, advancing the development of algal protein-based therapeutics. Full article

We report herein the development of a polyclonal antibody against ochratoxin A (OTA) using a specially designed synthetic OTA derivative as the immunizing hapten. This OTA derivative contains a tetrapeptide linker (glycyl-glycyl-glycyl-lysine, GGGK), through which it can be linked to a carrier protein and form an immunogenic conjugate. The OTA derivative (OTA-glycyl-glycyl-glycyl-lysine, OTA-GGGK) has been synthesized on a commercially available resin via the well-established Fmoc-based solid-phase peptide synthesis (Fmoc-SPPS) strategy; overall, this approach has allowed us to avoid tedious liquid-phase synthesis protocols, which are often characterized by multiple steps, several intermediate products and low overall yield. Subsequently, OTA-GGGK was conjugated to bovine thyroglobulin through glutaraldehyde, and the conjugate was used in an immunization protocol. The antiserum obtained was evaluated with a simple-format ELISA in terms of its titer and capability of recognizing the natural free hapten; the anti-OTA antibody, as a whole IgG fragment, was successfully applied to three different immunoanalytical systems for determining OTA in various food materials and wine samples, i.e., a multi-mycotoxin microarray bio-platform, an optical immunosensor, and a biotin–streptavidin ELISA, which has proved the analytical effectiveness and versatility of the anti-OTA antibody developed. The same approach may be followed for developing antibodies against other low-molecular-weight toxins and hazardous substances. Full article

Olive (Olea europaea) leaves, a by-product of olive oil production, represent a promising source of bioactive peptides. In this study, the peptidome of an olive leaf protein hydrolysate (OLPH) obtained via enzymatic hydrolysis with Alcalase was identified and analyzed for the first time. Liquid Chromatography coupled to Trapped Ion Mobility Spectrometry and Tandem Mass Spectrometry (LC-TIMS-MS/MS) analysis revealed over 7000 peptide sequences. Peptides with PeptideRanker scores above 0.79 were selected for in silico evaluation of antimicrobial potential, including physicochemical characterization and molecular docking. Several peptides—such as NYPAWGY, SSKGSLGGGF, QWDQGYF, and SGPAFNAGR—exhibited strong predicted antimicrobial potential, supported by favorable interactions with bacterial, viral, and fungal targets in docking simulations. Correlation analysis revealed that physicochemical features, such as net hydrogen, amphipathicity, and isoelectric point, were positively associated with predicted antimicrobial activity. These findings highlight the potential of olive leaf-derived peptides as natural antimicrobial agents and support the valorization of olive by-products as a sustainable source of functional ingredients for applications in food safety and health. Further experimental validation is needed to confirm the efficacy and mechanism of action of the identified peptides. Full article

Spinal muscular atrophy (SMA) is a severe neurodegenerative disorder that has an approved treatment that can still be improved. Antisense oligonucleotides (AONs) are currently delivered intrathecally for SMA therapy based on SMN2 gene splicing correction, and high concentrations are required to achieve an improvement of the disease symptoms. In this study, AONs were introduced into SMA fibroblast cell cultures by means of an arginine–histidine-rich peptide carrier that had been decorated with iRGD ligands. Due to the protected and receptor-mediated nature of AON delivery within these complexes, low concentrations can be used. We assessed the RNA-binding characteristics, cytotoxicity, size, and zeta potential of AON/carrier complexes as well as the efficiency of SMN2 gene splicing correction following transfections. After testing a variety of AON/carrier formulations, we selected those that produced the best outcomes. The AON/carrier complexes that were found to be the most effective significantly increased the proportion of full-length SMN transcripts and the quantity of nuclear gems. Thus, we demonstrated the potential of delivering therapeutic AONs into SMA cells using a ligand-modified peptide carrier. Full article

Background: Oxidative stress and inflammation are major drivers of metabolic inflammatory diseases, and natural antioxidant peptides represent promising therapeutic agents. Antioxidant peptides derived from Cyperus protein (CAOP) exhibit high digestibility and bioavailability, but their antioxidant and anti-inflammatory mechanisms remain unclear. Methods: We employed in vitro experiments, non-targeted metabolomics, peptide omics, and molecular docking techniques to explore how CAOP exerts dual antioxidant and anti-inflammatory effects. Results: The in vitro experiments showed that in LPS-induced RAW264.7 cells, CAOP not only significantly increased the levels of superoxide dismutase (SOD) and catalase (CAT) but also significantly reduced the gene expression and secretion of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as well as the phagocytic ability of cells. Metabolomics studies indicate that CAOP protects cells from LPS-induced damage by enhancing intracellular glutathione metabolism pathways, glyceraldehyde and dicarboxylic acid metabolism pathways, pantothenic acid and coenzyme A biosynthesis metabolism pathways, and thiamine metabolism pathways while inhibiting the ferroptosis pathway. CAOP was purified using Sephadex G-25 column chromatography, and its amino acid sequence was determined using LC-MS/MS technology. Subsequently, 25 peptide sequences were screened through bioinformatics analysis. These peptides can target Keap1. Among them, DLHMFVWS (-ICE = 62.8072) and LGHPWGNAPG (-ICE = 57.4345) are most likely to activate the Nrf2-Keap1 pathway. Conclusions: CAOP exerts antioxidant and anti-inflammatory effects by regulating the key metabolic networks, demonstrating its therapeutic promise for associated with oxidative damage and metabolic inflammation disorders. Full article

Several carrier proteins are involved in nuclear translocation from the cytoplasm to the nucleus in eukaryotic cells. We have previously demonstrated the binding of several intact folded and disordered proteins to the human isoform importin α3 (Impα3); furthermore, disordered peptides, corresponding to their nuclear localization signals (NLSs), also interact with Impα3. These proteins and their isolated NLSs also bind to the truncated importin species ∆Impα3, which does not contain the N-terminal disordered importin binding domain (IBB). In this work, we added a further ‘layer’ of conformational disorder to our studies, testing whether the isolated D-enantiomers of NLSs of selected proteins, either folded or unfolded, were capable of binding to both Impα3 and ∆Impα3. The D-enantiomers, like their L-form counterparts, were monomeric and disordered in isolation, as shown by nuclear magnetic resonance (NMR). We measured the ability of such D-enantiomeric NLSs to interact with both importin species by using fluorescence, biolayer interferometry (BLI), isothermal titration calorimetry (ITC), and molecular simulations. In all cases, the binding affinities were within the same range as those measured for their L-isomer counterparts for either Impα3 or ∆Impα3, and the binding locations corresponded to the major NLS binding site of the protein. Thus, the stereoisomeric nature is not important in defining the binding of proteins to the main component of classical cellular translocation machinery, although the primary structure of the hot-spot site for NLS binding of importin is well defined. Full article

Sulforaphane, a natural isothiocyanate predominantly found in cruciferous vegetables, has shown potential in preventing and treating Helicobacter pylori infection. However, the underlying metabolic mechanisms remain largely unclear. This study employed high-coverage metabolomics and lipidomics methods to comprehensively investigate the effects of sulforaphane on the serum and liver metabolic profiles of H. pylori-infected mice. Metabolomics and lipidomics analysis revealed that H. pylori infection disrupted multiple metabolic pathways, leading to perturbations in amino acids, fatty acids, bile acids, and various lipid species. Sulforaphane treatment can ameliorate these disruptions, notably reversing alterations in serum glycerophospholipids and restoring hepatic levels of amino acids, bile acids, glycerophospholipids, ceramides, and peptides. Key metabolic pathways implicated included glutathione metabolism and glycine and serine metabolism, which are associated with antioxidant defense and host resistance to pathogenic infections. These findings offer a comprehensive metabolic basis for understanding the therapeutic effects of sulforaphane against H. pylori infection. Full article

West Nile virus (WNV) is a mosquito-borne neurotropic virus that causes neurologic disease in both humans and horses. Yet the long-term cellular immune response following natural infection in horses remains poorly understood. This study aims to evaluate the WNV-specific T-cell response in horses recovered from West Nile neuroinvasive disease (WNND). Twelve client-owned horses (4 Hungarian sport horses, 2 Lippizaners, 1 KWPN, 1 Shagya Arabian, 1 Friesian, 1 Gidran, 1 Andalusian, and 1 draft cross horse) with confirmed clinical WNV infection were enrolled, and peripheral blood mononuclear cells (PBMCs) were collected approximately 290 days post infection. An equine interferon-gamma (IFNγ) Enzyme-Linked Immunospot (ELISpot) assay was performed using a WNV capsid peptide pool as an antigen to assess virus-specific cellular immunity. Results: Ten of twelve horses (83%) exhibited a significant IFNγ response. Statistical analyses revealed no association between ELISpot responses and clinical severity, age, sex, breed, or neutralizing antibody titers. These results demonstrate that naturally infected horses are capable of mounting robust WNV-specific T-cell responses independent of humoral immunity. The findings support a potentially important role for cellular immune memory in long-term protection against WNV reinfection and suggest that the capsid peptide-based ELISpot assay may serve as a useful diagnostic or research tool for the evaluation of orthoflavivirus immunity in equines. Full article

Staphylococcus shinii (S. shinii) is a coagulase-negative species primarily associated with the degradation of organic matter, contributing to nutrient cycling in natural environments. This species has been mainly studied in clinical and terrestrial contexts, with no previous reports of its presence in marine environments. In this study, we report the first isolation of S. shinii from a marine habitat. The strain SC-M1C was isolated from the Red Sea sponge Negombata magnifica. Whole-genome sequencing confirmed its taxonomic identity as S. shinii. The genome uncovers potential adaptive characteristics that facilitate survival in marine ecosystems, comprising genes associated with osmoregulation, nutrient acquisition, stress response, and resistance to heavy metals. Moreover, multiple genomic islands and plasmids were identified, suggesting a potential role in horizontal gene transfer and environmental adaptability. The presence of biosynthetic gene clusters linked to non-ribosomal peptides, siderophores, and terpene production indicates potential for biochemical versatility beyond traditional metabolic expectations. This study presents the first genomic insights into S. shinii in a marine context, highlighting its ecological significance and adaptive mechanisms in a high-salinity environment. These findings expand our understanding of staphylococcal ecology beyond terrestrial and clinical origins and provide a foundation for exploring the role of S. shinii in marine microbial interactions and environmental resilience. Full article

Kombucha, a fermented tea beverage, is gaining popularity due to its rich content of bioactive compounds and associated health benefits. Kombucha fermentation involves a complex microbial consortium, including acetic acid bacteria, lactic acid bacteria, and yeasts, that works synergistically to enhance its nutritional and functional properties. Key compounds produced during fermentation provide antioxidant, anti-inflammatory, and antimicrobial benefits. Despite its well-documented health-promoting properties, limited research exists on how human digestion influences the stability and functionality of kombucha bioactive components. This study investigated how digestion impacts kombucha made from green and black teas, focusing on free amino acid content, antioxidant activity, antimicrobial potential, and microbiota viability. Results showed that digestion significantly increased free amino acids, as fermentation released peptides suitable for gastrointestinal digestion. However, L-theanine, a beneficial tea compound, was no longer detectable after fermentation and digestion, suggesting limited bioaccessibility. Digested kombucha exhibited higher antioxidant activity and stronger antimicrobial effects compared to undigested tea. Moreover, culture-dependent and PMA-based sequencing confirmed the survival of viable microbial strains through simulated gastrointestinal conditions, suggesting the potential of kombucha as a source of live, functional microbes. These findings support the role of kombucha as a natural functional beverage whose health benefits not only persist but may be enhanced after digestion. Full article

The tumor suppressor DAB2IP, a RasGAP and cytoplasmic adaptor protein, modulates signal transduction in response to several extracellular stimuli, negatively regulating multiple oncogenic pathways. Accordingly, the loss of DAB2IP in tumor cells fosters metastasis and enhances chemo- and radioresistance. DAB2IP is rarely mutated in cancer but is frequently downregulated or inactivated by multiple mechanisms. Solid experimental evidence shows that DAB2IP reactivation reduces cancer aggressiveness in tumors driven by multiple different oncogenic mutations, making this protein an interesting target for cancer therapy. Considering this evidence, we screened a drug library to identify molecules that increase DAB2IP protein levels. We employed CRISPR/Cas9 gene editing to generate two prostate cancer cell models in which endogenous DAB2IP is fused to HiBiT, a peptide tag that enables luminescence-based detection of protein levels in a sensitive and quantitative manner. Using this approach, we identified drugs able to increase DAB2IP levels. We focused our attention on thiostrepton, a natural cyclic oligopeptide antibiotic that has been reported to inhibit the survival of various cancer cell lines. Functional experiments revealed that the cancer-inhibitory effect of thiostrepton is reduced in the absence of DAB2IP, suggesting that upregulation of this protein contributes to its action. These findings encourage further development of thiostrepton for the treatment of solid cancers and unveil a novel molecular target underlying its anti-tumoral activity. Full article

The rapid expansion of peptide libraries and the increasing functional diversity of peptides have highlighted the significance of predicting the multifunctional properties of peptides in bioinformatics research. Although supervised learning methods have made advancements, they typically necessitate substantial amounts of labeled data for yielding accurate prediction. This study presents MvAl-MFP, a multi-label active learning approach that incorporates multiple feature views of peptides. This method takes advantage of the natural properties of multi-view representation for amino acid sequences, meets the requirement of the query-by-committee (QBC) active learning paradigm, and further significantly diminishes the requirement for labeled samples while training high-performing models. First, MvAl-MFP generates nine distinct feature views for a few labeled peptide amino acid sequences by considering various peptide characteristics, including amino acid composition, physicochemical properties, evolutionary information, etc. Then, on each independent view, a multi-label classifier is trained based on the labeled samples. Next, a QBC strategy based on the average entropy of predictions across all trained classifiers is adopted to select a specific number of most valuable unlabeled samples to submit them to human experts for labeling by wet-lab experiments. Finally, the aforementioned procedure is iteratively conducted with a constantly expanding labeled set and updating classifiers until it meets the default stopping criterion. The experiments are conducted on a dataset of multifunctional therapeutic peptides annotated with eight functional labels, including anti-bacterial properties, anti-inflammatory properties, anti-cancer properties, etc. The results clearly demonstrate the superiority of the proposed MvAl-MFP method, as it can rapidly improve prediction performance while only labeling a small number of samples. It provides an effective tool for more precise multifunctional peptide prediction while lowering the cost of wet-lab experiments. Full article

Avian influenza A viruses (IAVs) pose a persistent threat to the poultry industry, causing substantial economic losses. Although traditional vaccines have helped reduce the disease burden, they typically rely on multivalent antigens, emphasize humoral immunity, and require intensive production. This study aimed to establish a genetically matched host–cell system to evaluate antigen-specific immune responses and identify conserved CD8+ T cell epitopes in avian influenza viruses. To this end, we developed an MHC class I genotype (B21)-matched host (Lohmann VALO SPF chicken) and cell vector (DF-1 cell line) model. DF-1 cells were engineered to express the hemagglutinin (HA) gene of clade 2.3.4.4b H5N1 either transiently or stably, and to stably express the matrix 1 (M1) and nucleoprotein (NP) genes of A/chicken/South Korea/SL20/2020 (H9N2, Y280-lineage). Following prime-boost immunization with HA-expressing DF-1 cells, only live cells induced strong hemagglutination inhibition (HI) and virus-neutralizing (VN) antibody titers in haplotype-matched chickens. Importantly, immunization with DF-1 cells transiently expressing NP induced stronger IFN-γ production than those expressing M1, demonstrating the platform’s potential for differentiating antigen-specific cellular responses. CD8+ T cell epitope mapping by mass spectrometry identified one distinct MHC class I-bound peptide from each of the HA-, M1-, and NP-expressing DF-1 cell lines. Notably, the identified HA epitope was conserved in 97.6% of H5-subtype IAVs, and the NP epitope in 98.5% of pan-subtype IAVs. These findings highlight the platform’s utility for antigen dissection and rational vaccine design. While limited by MHC compatibility, this approach enables identification of naturally presented epitopes and provides insight into conserved, functionally constrained viral targets. Full article

Collagen type I (COL(I)) is a key component of the extracellular matrix (ECM) and is involved in cell signaling and migration through cell receptors. Collagen degradation produces bioactive peptides (matrikines), which influence cellular processes. In this study, we investigated the biological effects of nine most abundant, naturally occurring urinary COL(I)-derived peptides on human endothelial cells at physiological concentrations, using cell migration assays, mass spectrometry-based proteomics, flow cytometry, and AlphaFold 3. While none of the peptides significantly altered endothelial migration by themselves at physiological concentrations, full-length COL(I) increased cell migration, which was inhibited by Peptide 1 (²²⁹NGDDGEAGKPGRPGERGPpGp²⁴⁹). This peptide uniquely contains the DGEA and GRPGER motifs, interacting with integrin α2β1. Flow cytometry confirmed the presence of integrin α2β1 on human endothelial cells, and AlphaFold 3 modeling predicted an interaction between Peptide 1 and integrin α2. Mass spectrometry-based proteomics investigating signaling pathways revealed that COL(I) triggered phosphorylation events linked to integrin α2β1 activation and cell migration, which were absent in COL(I) plus peptide 1-treated cells. These findings identify Peptide 1 as a biologically active COL(I)-derived peptide at a physiological concentration capable of modulating collagen-induced cell migration, and provide a foundation for further investigation into its mechanisms of action and role in urine excretion. Full article