Search Results (614)

Bioactive peptides encrypted in bovine β-casein display diverse physiological functions, including antihypertensive, antioxidative, antimicrobial, and immunomodulatory activities. These peptides are normally released during gastrointestinal digestion or microbial fermentation, especially by proteolytic systems of lactic acid bacteria (LAB). However, peptide yields vary widely among LAB strains, reflecting strain-specific protease repertoires. To overcome these limitations, the scientific goal of this study is to provide a comprehensive synthesis of how synthetic biology, molecular biotechnology, and systems-level approaches can be leveraged to enhance the targeted discovery and production of β-casein-derived bioactive peptides. Genome engineering tools such as clustered regularly interspaced short palindromic repeats associated system (CRISPR/Cas) systems have been applied to modulate gene expression and metabolic flux in LAB, while inducible expression platforms allow on-demand peptide production. Additionally, cell-free systems based on LAB lysates further provide rapid prototyping for high-throughput screening. Finally, multi-omics approaches, including genomics, transcriptomics, proteomics, and metabolomics, further help pinpoint regulatory bottlenecks and facilitate rational strain optimization. This review provides a comprehensive overview of bioactive peptides derived from bovine β-casein and highlights recent progress in LAB-based strategies—both natural and engineered—for their efficient release. These advances pave the way for developing next-generation functional fermented foods enriched with targeted bioactivities. Full article

The increasing global burden of mosquito-borne diseases and the widespread development of insecticide resistance in mosquitoes have fueled renewed interest in entomopathogenic fungi as effective tools that are compatible with existing mosquito control strategies. These fungi produce different types of infective propagules, including hydrophobic conidia and yeast-like blastospores, which differ in structure, mode of infection, and virulence. In this study, we evaluated the larvicidal activity of conidial and blastospore propagules from Beauveria bassiana MBC076 and Beauveria brongniartii MBC397 against Aedes aegypti. Conidia exhibited more rapid and more potent larvicidal effects compared to blastospores, but the overall survival at seven days post-infection was similar between the two types of propagules. Interestingly, B. brongniartii blastospore infections resulted in a significantly higher proportion of pupal mortality, suggesting a delayed mode of action. Immune profiling of infected larvae indicated significant induction of antimicrobial effectors such as cecropin, defensin, and attacin, primarily in response to conidial infection. In contrast, blastospore infections were associated with reduced expression of several prophenoloxidase genes, particularly during infection with B. brongniartii blastospores. These findings indicate that different fungal species and their propagule types exert varying levels of virulence and immune modulation in mosquito larvae. This study provides insights into the infection dynamics of fungal propagules and identifies immune markers that can be leveraged to enhance the efficacy of fungal-based larvicides. Full article

A new Schiff base, (E)-2-(((1,10-phenanthrolin-5-yl)imino)methyl)-4,6-di-tert-butylphenol (Fen-IHB), was designed to incorporate an intramolecular hydrogen bond (IHB) between the phenolic OH and the azomethine nitrogen with the goal of modulating its physicochemical and biological properties. Fen-IHB was synthesized by condensation of 5-amino-1,10-phenanthroline with 3,5-di-tert-butyl-2-hydroxybenzaldehyde and exhaustively characterized by HR-ESI-MS, FTIR, 1D/2D NMR (¹H, ¹³C, DEPT-45, HH-COSY, CH-COSY, D₂O exchange), and UV–Vis spectroscopy. Cyclic voltammetry in anhydrous CH₃CN revealed a single irreversible cathodic peak at −1.43 V (vs. Ag/Ag⁺), which is consistent with the intramolecular reductive coupling of the azomethine moiety. Density functional theory (DFT) calculations, including MEP mapping, Fukui functions, dual descriptor analysis, and Fukui potentials with dual descriptor potential, identified the exocyclic azomethine carbon as the principal nucleophilic site and the phenolic ring (hydroxyl oxygen and adjacent carbons) as the main electrophilic region. Noncovalent interaction (NCI) analysis further confirmed the strength and geometry of the intramolecular hydrogen bond (IHB). In vitro antimicrobial assays indicated that Fen-IHB was inactive against Gram-negative facultative anaerobes (Salmonella enterica serovar Typhimurium and Typhi, Escherichia coli) and strictly anaerobic Gram-positive species (Clostridioides difficile, Roseburia inulinivorans, Blautia coccoides), as any growth inhibition was indistinguishable from the DMSO control. Conversely, Fen-IHB displayed measurable activity against Gram-positive aerobes and aerotolerant anaerobes, including Bacillus subtilis, Streptococcus pyogenes, Enterococcus faecalis, Staphylococcus aureus, and Staphylococcus haemolyticus. Overall, these comprehensive characterization results confirm the distinctive chemical and electronic properties of Fen-IHB, underlining the crucial role of the intramolecular hydrogen bond and electronic descriptors in defining its reactivity profile and selective biological activity. Full article

Micromeria graeca (L.) Benth. ex Rchb. (Lamiaceae) is a promising medicinal plant valued for its antioxidant, anti-hyperglycemic, anti-hypertensive, antimicrobial, and anti-aflatoxigenic properties. It is rich in phenolic and flavonoid compounds, supporting its traditional use for digestive, respiratory, cardiovascular, and dermatological conditions. Plant tissue culture facilitates controlled in vitro propagation to study plant growth and bioactive properties. The effects of activated charcoal and varying subculture intervals on multiplication and biomass production in M. graeca shoot cultures were investigated. The phenolic composition of methanolic extracts from in vitro-grown plants was characterized using high-performance liquid chromatography (HPLC), identifying rosmarinic, caffeic, and syringic acids as the primary phenolic compounds. Antimicrobial activity against selected microbial strains was evaluated using a micro-well dilution assay. Anticancer activity of selected extracts was assessed in human hepatocellular carcinoma cell line HepG2, with flow cytometry (Annexin-V/PI staining) used to analyze cell death mechanisms, and compared to pure rosmarinic acid (RA). Activated charcoal showed no beneficial effects on multiplication or biomass production, but significantly increased phenolic acid content (up to 4-fold). RA dominated the phenolic profiles, with other phenolic acids present in lower amounts. Methanolic extracts exhibited negligible antimicrobial activity compared to reference antibiotics and fungicide. Extracts from 4-week-old shoot cultures displayed modest anti-hepatoma activity (IC50 values of CV assay ranging from 193 to 274 µg mL⁻¹), inducing HepG2 cell apoptosis via oxidative stress, independent of RA. Our results suggest that the metabolic output of M. graeca shoot cultures and consequently their biological activity can be modulated by varying in vitro culture conditions. These findings underscore the potential of their methanolic extracts for biotechnological production and therapeutic applications. Full article

Propolis is a complex, resinous substance originating from plant exudates and processed by bees, e.g., Apis mellifera L. Propolis is rich in flavonoids, phenolic acids, and terpenoids. It exhibits broad biological activities, including antimicrobial, anti-inflammatory, immunomodulatory, and anticancer effects. This review summarizes recent findings on the therapeutic potential of propolis in preclinical models of cancer and infectious diseases, with a focus on its molecular mechanisms of action. Experimental data indicate that propolis and its active constituents can induce apoptosis, inhibit proliferation, angiogenesis, and metastasis of cancer cells, and modulate immune responses and microbial virulence. Despite promising in vitro results, in vivo studies remain limited, and their results are often inconsistent. The variability in chemical composition due to geographical and botanical factors, as well as the lack of standardized extracts, further impedes translational research. We highlight key molecular pathways affected by propolis and propose directions for future studies, including improved standardization and more rigorous in vivo results description. These efforts are essential to validate propolis as a potential booster or alternative therapeutic strategy in oncology and infectious diseases treatment. Full article

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

Lactoferrin (Lf) is a multifunctional iron-binding glycoprotein of the transferrin family that plays a central role in host defense, particularly in protection against infection and tissue injury. Abundantly present in colostrum, secretory fluids, and neutrophil granules, Lf exerts broad-spectrum antimicrobial activity against bacteria, viruses, fungi, and parasites. These effects are mediated by iron sequestration, disruption of microbial membranes, inhibition of microbial adhesion, and interference with host–pathogen interactions. Beyond its antimicrobial functions, Lf regulates pro- and anti-inflammatory mediators and mitigates excessive inflammation. Additionally, Lf alleviates oxidative stress by scavenging reactive oxygen species and enhancing antioxidant enzyme activity. This review summarizes the current understanding of Lf’s biological functions, with a particular focus on its roles in microbial infections, immune modulation, oxidative stress regulation, and inflammation. These insights underscore the therapeutic promise of Lf as a natural, multifunctional agent for managing infectious and inflammatory diseases and lay the groundwork for its clinical application in immune-related disorders. Full article

Biofilms are complex microbial communities embedded in a self-produced extracellular polymeric matrix. These structures confer increased resistance/tolerance to antimicrobial agents and immune responses, posing a serious challenge in both clinical and industrial contexts. In response to these challenges, increasing attention has been given to the development of novel antibiofilm strategies. Among the promising alternatives are lectins—carbohydrate-binding proteins. This review explores the structural and functional features of biofilms and critically discusses recent studies reporting the antibiofilm effects of lectins. Additionally, it addresses the main challenges and limitations surrounding the practical application of lectins to combat biofilms. Lectins from plants, animals, and microorganisms have shown potential to inhibit biofilm formation by disrupting the extracellular matrix, modulating quorum sensing, and affecting bacterial motility and metabolism. Additionally, they can eradicate established biofilms by degrading the matrix, killing or removing microbial cells, and/or preventing biofilm reformation. Together, the findings reviewed here support the continued investigation of lectins as potential agents against biofilm-associated infections as well as highlight the need to address existing gaps, such as the lack of in vivo studies and limited research on the structure–function relationships of lectins and their antibiofilm activity. Full article

Nowadays, members of the genus Enterobacter have been documented as human and aquaculture pathogens. To date, no reports have described Enterobacter bugandensis infecting Hippocampus abdominalis. In the present study, an isolate of E. bugandensis, designated H4, was identified as a causative pathogen in cultured H. abdominalis following Koch’s postulate, and its virulence properties were further described. The isolate’s genome consisted of a single circular chromosome and harbored several virulence and resistance genes, including, but not limited to, csgG, acrB, hcp, gndA, galF, rpoS, fur, rcsB, and phoP involved in adherence, antimicrobial activity, effector delivery systems, immune modulation, and regulation, as well as baeR, blaACT-49, ramA, hns, ftsI, acrA, gyrA, fabI, crp, oqxB, parE, gyrB, phoP, rpoB, tuf, ptsI, and fosA2 functioning against aminoglycoside, cephamycin, disinfecting agent and antiseptic, fluoroquinolone, macrolide, peptide, and other antimicrobials. Additionally, the isolate exhibited multiple resistance to cephalosporins, penicillins, and tetracyclines and demonstrated a median lethal dose (LD₅₀) of 4.47 × 10⁵ CFU/mL in H. abdominalis. To our knowledge, this is the first study to describe E. bugandensis infecting H. abdominalis. These findings highlight the zoonotic potential of E. bugandensis and underscore the need for targeted health management in seahorse farming. Full article

Background/Objectives: Antimicrobial peptides (AMPs) have emerged as promising alternatives to conventional antibiotics in livestock, offering a sustainable strategy for controlling bacterial pathogens in food production systems. In addition to their direct antimicrobial effects, AMPs play a key role in modulating host-associated microbiomes, influencing both microbial composition and function. Advances in metagenomic sequencing and bioinformatic tools now enable comprehensive exploration of AMP diversity and activity within complex microbial ecosystems. Methods: In this study, we employed Illumina-based next-generation sequencing (NGS) to analyze intestinal contents from six gut sections of broiler chickens obtained from a Spanish slaughterhouse. Results: Through de novo assembly and bioinformatic annotation, we identified biosynthetic gene clusters (BGCs) encoding ribosomally synthesized and post-translationally modified peptides (RiPPs), other specialized bioactive secondary metabolites, antimicrobial resistance genes (ARGs), virulence factor genes (VFGs), and a diverse microbial community. Among all gut sections, the cecum exhibited the highest genetic richness, characterized by a high diversity of RiPP-like clusters and antimicrobial resistance determinants. Conclusions: These findings highlight the poultry gut, particularly the cecum, as a significant reservoir of antimicrobial peptides (AMPs) with potential implications in antibiotic-free poultry production and enhanced food safety. Full article

Melanin overproduction contributes to hyperpigmentation disorders such as melasma and solar lentigines, leading to increasing demand for safe and effective skin-lightening agents. D-cycloserine (DCS), a known antimicrobial agent, has not been previously evaluated for dermatological applications. This study aimed to explore the potential of DCS as a novel anti-melanogenic compound and to elucidate its underlying molecular mechanisms in melanogenesis inhibition. The cytotoxicity and anti-melanogenic effects of DCS were assessed in B16F10 melanoma cells stimulated with α-MSH. Cell viability was determined via MTT assays, while melanin content, tyrosinase activity, and the expression levels of MITF, TYR, TRP-1, TRP-2, and major signaling proteins (e.g., CREB, MAPKs, GSK-3β/β-catenin) were evaluated using colorimetric assays and Western blotting. A 3D human skin model was also used to confirm in vitro findings, and a primary skin irritation test was conducted to assess dermal safety. DCS significantly reduced α-MSH-induced melanin content and tyrosinase activity without cytotoxicity at concentrations ≤100 µM. It downregulated MITF and melanogenic enzyme expression and modulated signaling pathways by enhancing ERK activation while inhibiting CREB, JNK, and p38 phosphorylation. Additionally, DCS suppressed β-catenin stabilization via GSK-3β activation. These effects were confirmed in a 3D human skin model, and a clinical skin irritation study revealed no adverse reactions in human volunteers. DCS exerts its anti-melanogenic effect by targeting multiple pathways, including CREB/MITF, MAPK, and GSK-3β/β-catenin signaling. Its efficacy and safety profiles support its potential as a novel cosmeceutical agent for the treatment of hyperpigmentation. Further clinical studies are warranted to confirm its therapeutic utility in human skin pigmentation disorders. Full article

Persistent type I interferon (IFN-I) signaling compromises adaptive anti-HIV-1 T cell immunity and promotes viral reservoir persistence, yet its effects on innate lymphoid cells during chronic infection remain unclear. Through integrated single-cell RNA sequencing and functional validation in HIV-1-infected humanized mice with combination antiretroviral therapy (cART) and IFN-I signaling blockade, we reveal IFN-I-induced dysfunction of natural killer (NK) cells and group 3 innate lymphoid cells (ILC3s). Mechanistically, the IFN-I-CD9 axis drives NK cells toward a decidual NK cell-like phenotype, impairing their cytotoxic activity. Furthermore, IFNAR blockade rescues ILC3 functionality, which is critical for IL-17/IL-22-mediated antimicrobial defense and mucosal barrier maintenance. Our study delineates IFN-I-driven immunosuppression across innate lymphocyte compartments and proposes the targeted modulation of this pathway to enhance antiviral and mucosal immunity in HIV-1 management. Full article

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) remains a critical public health concern due to its multidrug resistance and capacity to form persistent infections, particularly in the context of implanted medical devices. Alternative therapeutic strategies that target bacterial virulence instead of viability are increasingly explored. This study aimed to evaluate the antimicrobial and antivirulence activity of an extract derived from Lacticaseibacillus rhamnosus CRL 2244 against two MRSA strains—USA300 and M86—and to elucidate its effects on bacterial physiology and gene expression under host-mimicking conditions. Methods: Antimicrobial activity was assessed using agar diffusion, MIC, and time-kill assays. Scanning electron microscopy of cells exposed to the extract confirmed decreased cellular density and morphological changes. Phenotypic assays evaluated biofilm formation, staphyloxanthin production, and adhesion to fibronectin. RT-qPCR analyzed transcriptional responses. Viability was assessed in the presence of human serum and type I collagen. Results: The CRL 2244 extract demonstrated bactericidal activity with up to 6-log₁₀ CFU/mL reduction at 1× MIC. In USA300, the extract reduced the expression of hla, lukAB, fnbA, and icaA, correlating with decreased staphyloxanthin levels. In M86, a significant reduction in biofilm formation and repression of lukAB, nucA, and fnbA were observed. Adhesion to fibronectin was impaired in both strains. The extract showed no cytotoxicity in human serum but reduced viability in collagen-enriched conditions. Conclusions: The Lcb. rhamnosus CRL 2244 extract modulates MRSA virulence in a strain-specific manner, targeting key regulatory and structural genes without inducing cytotoxic effects. Full article

Green synthesis of gold nanoparticles (AuNPs) provides a significantly eco-friendly and low-impact counterpart to conventional chemical methods. In the present study, we synthesized gold nanoparticles using Schinus molle (P-AuNPs) aqueous extract as a reducing and stabilizing agent. The obtained nanoparticles were then stabilized by another biocompatible agent, the chiral amino acids L-cysteine (L-Cys-AuNPs) and D-cysteine (D-Cys-AuNPs), to estimate the potential of the surface modification for enhancing AuNPs surface chemistry and antimicrobial action. The synthesized gold nanoparticles were confirmed by UV-Vis spectroscopy, FTIR, XRD, and circular dichroism to validate their formation, crystalline structure, surface properties, and chirality. Physicochemical characterization confirmed the formation of crystalline AuNPs with size and morphology modulated by chiral functionalization. TEM and DLS analyses showed that L-cysteine-functionalized AuNPs were smaller and more uniform, while FTIR and circular dichroism spectroscopy confirmed surface binding and the induction of optical activity, respectively. L-Cys-AuNPs exhibited the highest antimicrobial efficacy against a broad spectrum of microorganisms, including Escherichia coli, Salmonella enterica, Listeria monocytogenes, Staphylococcus aureus, Staphylococcus epidermidis, and, notably, Candida albicans. L-Cys-AuNPs showed the lowest MIC and MBC values, highlighting the synergistic effect of chirality on biological performance. These findings suggest that L-cysteine surface engineering significantly enhances the therapeutic potential of AuNPs, particularly in combating drug-resistant fungal pathogens such as C. albicans. This research paves the way for the development of next-generation antimicrobial agents, reinforcing the relevance of green nanotechnology in the field of materials science and nanotechnology. Full article

The global rise in antimicrobial resistance poses a major threat to public health, with multidrug-resistant bacterial infections expected to surpass cancer in mortality by 2050. As traditional antibiotic pipelines stagnate, novel therapeutic alternatives are critically needed. Antimicrobial peptides (AMPs), particularly those derived from marine organisms, have emerged as promising antimicrobial candidates due to their broad-spectrum activity, structural diversity, and distinctive mechanisms of action. Unlike conventional antibiotics, AMPs can disrupt microbial membranes, inhibit biofilm formation, and even modulate immune responses, making them highly effective against resistant bacteria. This review highlights the potential of marine AMPs as next-generation therapeutics, emphasizing their efficacy against multidrug-resistant pathogens and biofilm-associated infections. Furthermore, marine AMPs show promise in combating persister cells and disrupting quorum sensing pathways, offering new strategies for tackling chronic infections. Despite their potential, challenges such as production scalability and limited clinical validation remain; nevertheless, the use of new technologies and bioinformatic tools is accelerating the discovery and optimization of these peptides, paving the way for bypassing these challenges. This review consolidates current findings on marine AMPs, advocating for their continued exploration as viable tools in the fight against antimicrobial resistance. Full article