Search Results (3,841)

Insects are continuously exposed to diverse microorganisms, including symbionts and pathogens, and rely on pattern-recognition receptors (PRRs) to initiate innate immune responses. Gram-negative bacteria-binding proteins (GNBPs) constitute an important class of the pivotal PRRs in insect immunity. However, whether GNBPs participate in immune responses against taxonomically distinct pathogens remains poorly understood. Red palm weevil (RPW), Rhynchophorus ferrugineus, is a notorious stem-boring insect pest that has caused huge economic loss worldwide. Our preliminary data indicated that the expression of RfGNBP5 could be induced dramatically upon the challenge of non-entomopathogenic bacteria Escherichia coli, Staphylococcus aureus and entomopathogenic fungus Beauveria bassiana. Here, it has been found that RfGNBP5 only possesses two conserved domains, a signal peptide and an intact glycoside hydrolase 16 (GH16) domain, but without the canonical carbohydrate-binding module (CBM39), implying that it might mediate insect immunity via its hydrolytic activity. RT-qPCR revealed that RfGNBP5 was expressed at the highest level in the hemolymph compared with other tissues and was significantly upregulated after exposure to pathogens, such as Escherichia coli, Staphylococcus aureus and Beauveria bassiana. Furthermore, the knockdown of RfGNBP5 potentiated the clearance efficiency of hemolymph against the invading pathogenic bacteria and fungi by increasing the expression level of two antimicrobial peptide genes, including RfAttacin in fat body and RfColeoptericin in gut, and augmenting the phenoloxidase (PO) activity in hemolymph. Taken together, these results suggested that RfGNBP5 acts as a negative regulator of RPW immunity, and it might be a potential candidate for further evaluation in RNAi-based pest management. Full article

Insect antimicrobial peptides (AMPs) are classically viewed as terminal effectors of innate immunity, but emerging evidence suggests that some can also shape defined neural states. In this Review, we argue that insect systems provide a powerful framework for resolving immune–brain communication at the level of individual peptide effectors, because genetically tractable innate-immune pathways allow pathway activation to be distinguished from peptide-specific effector function. Rather than surveying AMP families exhaustively, we focus on representative cases in which peptide identity, source, and timing can be linked to sleep, memory-related plasticity, and responses to acute injury. These studies show that the neural consequences of AMP induction cannot be inferred from pathway activation alone, but require peptide-level analysis of effector identity, cellular context, and exposure logic. This perspective also raises the question of translational potential. At present, direct biomedical development of endogenous insect AMPs in neural contexts remains limited, whereas more tangible applied interest has centered on insect venom peptides that share AMP-like physicochemical features. We therefore discuss insect venoms separately from endogenous AMP physiology. Venom peptides are not physiological equivalents of endogenous insect AMPs, but represent evolutionarily diversified AMP-like templates for scaffold discovery, mechanistic probing, and therapeutic engineering. Together, this review develops a peptide-level perspective on insect neuroimmune biology while highlighting insect venoms as a valuable, but highly constrained, source of templates for biomedical discovery. Full article

Alcohol-related liver disease (ALD) poses a significant global health burden, driven by complex mechanisms including oxidative stress, inflammation, and gut–liver axis disruption. While the individual roles of gut microbiota dysbiosis and ageing in ALD pathogenesis are increasingly recognized, their synergistic interaction remains poorly understood. This review synthesizes current evidence to argue that there is an interaction between ageing and the gut microbiota that collectively amplifies progression of ALD. Specifically, ageing promotes gut dysbiosis through immunosenescence (e.g., reduced IgA diversification and antimicrobial peptide decline), intestinal barrier failure, and altered microbial metabolite profiles (e.g., decreased short-chain fatty acids and dysregulated bile acid metabolism). Conversely, dysbiosis-derived metabolites and endotoxins modulate ageing-related signaling pathways, including SIRT1, FOXO, and Nrf2, thereby accelerating hepatic cellular senescence, inflammation, and fibrogenesis. Furthermore, we also discussed the typical microbial changes in ALD. These include an increase in the Proteobacteria, a decrease in the Bacteroidetes, as well as imbalances in fungi and viruses. In ageing, similar but distinct shifts occur, such as reduced microbial diversity, decreased short-chain fatty acid producers, and increased intestinal permeability. Therapeutic strategies targeting the gut microbiota (probiotics, fecal microbiota transplantation) or ageing-related pathways (SIRT1 activators) hold promise. Future research priorities include validating ageing-associated microbial signatures as predictors of ALD progression and testing microbiota-targeted interventions in aged preclinical models. Collectively, this review identifies the microbiota–ageing axis as a tractable therapeutic target for ALD and provides a framework for future mechanistic and translational studies. Full article

Discovery of new antibiotic candidates is driven by urgent global health needs and evolving resistance to current treatments. In pursuit of novel peptide-based antibiotics, more than 100 dipeptides containing fluorinated phenylalanine (F-Phe) residues were synthesized by undergraduate researchers at eight institutions and evaluated against Pseudomonas aeruginosa (P. aeruginosa) in a primary biofilm formation assay. Inclusion of multistep synthesis experiments in curricular laboratory courses at different institutions prompted the prioritization of robust and adaptable procedures that were effective at generating large compound sets for study. Several dipeptides were identified that inhibited biofilm formation at concentrations of 1 μg/mL or less. Further study of two of them, (S,S)-4-F-Phe-Ala and (S,S)-3,4-diF-Phe-Ala, revealed two distinct biological profiles. Inhibition of biofilm formation by (S,S)-4-F-Phe-Ala was directly associated with growth inhibition. In contrast, (S,S)-3,4-diF-Phe-Ala did not significantly inhibit bacterial growth at concentrations up to 100 μg/mL. Mammalian cell lines treated with either dipeptide at much higher concentrations remained viable, demonstrating selective toxicity for P. aeruginosa. Taken together, these data indicate that dipeptides comprising F-Phe are promising leads for the discovery of new antibiofilm therapeutics. Full article

Chronic wounds represent a growing global healthcare burden driven by persistent inflammation, polymicrobial biofilm formation, impaired tissue regeneration, and increased antimicrobial resistance. This review examines the mechanistic interplay between chronic wound pathophysiology, biofilm persistence, and antimicrobial peptide (AMP)-based therapeutics, with particular emphasis on translational barriers and advanced biomaterial-enabled delivery strategies. Current evidence demonstrates that AMPs exert multifactorial activities extending beyond direct antimicrobial effects, including membrane disruption, quorum-sensing inhibition, extracellular polymeric substance (EPS) destabilization, immune modulation, angiogenic stimulation, and promotion of re-epithelialization. However, their clinical translation remains limited due to proteolytic degradation, poor stability, cytotoxicity, rapid clearance, and inadequate retention within the hostile chronic wound microenvironment. To address these limitations, emerging biomaterial platforms—including hydrogels, electrospun nanofibers, nanoparticles, self-assembling peptide systems, and stimuli-responsive smart dressings—have been developed to improve AMP stability, controlled release, biofilm penetration, and regenerative efficacy. This review further highlights current preclinical and clinical challenges, including the lack of standardized polymicrobial biofilm models and translationally relevant wound systems, while discussing future perspectives such as artificial intelligence-assisted peptide design and precision wound therapeutics. We argue that peptide discovery is no longer the principal bottleneck: the rate-limiting steps are now peptide stabilization, biofilm-targeted delivery, and dosing, and no current platform yet couples validated eradication of mature polymicrobial biofilms with validated tissue regeneration in a clinically representative model. Collectively, AMP-enabled smart biomaterials may support the transition from passive wound management toward responsive, biofilm-targeted regenerative therapy. Full article

Background/objectives: Foodborne diseases remain a significant global public health concern, requiring innovative and effective antimicrobial strategies to control food pathogens. Encapsulation of natural antimicrobials have attracted increasing interest. In this study, liposomes encapsulating pink pepper essential oil (PPEO), nisin, or their combination were developed, aiming to potentiate antimicrobial performance against foodborne pathogens. Methods: Phosphatidylcholine liposomes were prepared by the thin-film method and characterized by DLS and FTIR. The antimicrobial activity of nisin, PPEO, and liposomes was investigated by the agar diffusion method against foodborne pathogens like Staphylococcus aureus, Listeria monocytogenes, and Salmonella Typhimurium. Results: The liposomes exhibited nanometric size ranging from 91 to 107 nm, low polydispersity, and zeta potential between −3.73 and −7.39 mV, indicating well-defined vesicles with negative surface charges. Encapsulation enhanced antimicrobial efficacy, with nisin–PPEO liposomes stored for 21 days under refrigeration showing a sustained inhibition of L. monocytogenes, outperforming liposomes containing nisin alone. The combined antimicrobials also inhibited Gram-positive bacteria in milk agar, used as a simulated food system. Additionally, the antioxidant activity of PPEO was preserved upon encapsulation, especially under refrigeration, reinforcing the protective role of the liposomes. Conclusions: The co-encapsulation approach strengthened the stability and bioactivity of natural antimicrobials, highlighting liposomal delivery as a promising strategy to control foodborne bacteria. Full article

Teixobactin is a promising antibiotic that targets cell wall biosynthesis in Gram-positive bacteria and displays a low propensity for resistance; however, its structural complexity presents challenges for analogue development and optimisation. In this study, we investigated the effects of macrocycle size and replacement of the native depsipeptide linkage with an amide bond on antibacterial activity using a simplified Leu₁₀-teixobactin scaffold. An amide-based macrocyclisation strategy was developed for efficient lactam formation using readily accessible amino acid building blocks, avoiding reliance on synthetically demanding modified diamino acids employed in other approaches. Two complementary synthetic routes provided access to a series of ten analogues, comprising linear and macrocyclised variants with systematic variation at position 8. Antibacterial activity was evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant clinical isolates. While linear analogues exhibited weak or no measurable antibacterial activity, macrocyclised analogues retained measurable antibacterial activity, indicating that macrocyclisation is essential within this scaffold, whereas moderate expansion of the macrocycle was tolerated. The structure–activity relationships identified here demonstrate the suitability of a simplified Leu₁₀-teixobactin framework and provide a platform for further optimisation of teixobactin-inspired antibiotics. Full article

Sepsis is a life-threatening syndrome characterized by a dysregulated host response to infection and progressive organ dysfunction. Although early antimicrobial therapy, source control, hemodynamic resuscitation, and organ support remain the foundations of care, these approaches do not directly reverse the cellular mechanisms that connect systemic inflammation to multi-organ failure. Mitochondrial dysfunction has emerged as a central mechanism linking impaired oxygen utilization, oxidative and nitrosative stress, immune-cell metabolic reprogramming, inflammatory amplification, and organ injury. During sepsis, inflammatory mediators, nitric oxide, microcirculatory abnormalities, calcium dysregulation, and metabolic stress converge on mitochondria, impairing oxidative phosphorylation and promoting mitochondrial reactive oxygen species/reactive nitrogen species (ROS/RNS) generation. When mitochondrial quality-control programs, including fission, fusion, mitophagy, and mitochondrial biogenesis, fail to restore network integrity, damaged mitochondria accumulate and become persistent sources of oxidative stress and danger signals. Mitochondrial damage-associated molecular patterns, particularly mitochondrial DNA, oxidized mitochondrial DNA, cardiolipin, ATP, and N-formyl peptides, activate innate immune pathways such as TLR9-MyD88-NF-kappaB, the NLRP3 inflammasome, and cGAS-STING signaling. In parallel, mitochondrial metabolism shapes macrophage activation, neutrophil function, T-cell competence, pyruvate-lactate handling through the pyruvate dehydrogenase complex, and the transition between hyperinflammation and immunosuppression. Clinical translation remains challenging because sepsis is biologically heterogeneous and mitochondrial dysfunction is dynamic, tissue-specific, and influenced by disease stage. This review synthesizes current knowledge on mitochondrial dysfunction in sepsis, emphasizing oxidative and nitrosative stress, mitochondrial quality control, mitochondrial damage-associated molecular pattern (DAMP) signaling, immunometabolism, organ-specific injury, candidate biomarkers, clinical translational strategies for mitochondria-targeted therapy, and future approaches based on multi-omics and artificial intelligence-assisted patient stratification. We argue that future therapeutic development should move beyond nonspecific antioxidant supplementation toward time-sensitive, phenotype-informed, and biomarker-guided mitochondrial medicine. Full article

Peptide therapeutics offer high target selectivity and low toxicity, but their clinical utility remains constrained by rapid proteolysis in vivo and negligible oral bioavailability. Incorporating non-canonical amino acids (ncAAs) provides a robust molecular engineering framework to overcome these pharmacokinetic bottlenecks. This review analyzes the structural and biophysical design rules of ncAA-mediated peptide stabilization, categorizing them into side-chain steric shielding, backbone conformational constraint, and stereochemical evasion of L-specific proteases. We systematically evaluate the biosynthetic milestones enabling this field, focusing on engineered orthogonal translation systems (tRNA/synthetase pairs, orthogonal ribosomes, quadruplet codons) and metabolic engineering strategies that supply fluorinated and other ncAA precursors de novo. Furthermore, we examine the translation of these technologies into clinical candidates (e.g., modified antimicrobial peptides, antibody–drug conjugates, and PROTACs) and identify scaling, immunogenicity, and computational modeling as key bottlenecks. This review serves as a technical reference for designing next-generation, hyper-stable peptide therapeutics. Full article

Six lactic acid bacteria isolated from São Jorge PDO cheese were characterised for technological, safety, antimicrobial, and probiotic properties. All isolates fermented a broad range of carbohydrates and lacked lipolytic activity, while SJC115 and SJC119 showed proteolysis. Safety profiling (γ-haemolysis, no DNase or gelatinase activity, and generally favourable antibiotic susceptibility) is promising, but tetracycline resistance warrants caution and genomic confirmation. L. paracasei and L. brevis isolates inhibited a wide range of foodborne pathogens (Listeria monocytogenes, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, Bacillus spp.) and spoilage fungi (Penicillium and Aspergillus spp.). Notably, two isolates (SJC117 and SJC120) exhibited antibacterial activity in neutralized cell-free supernatants, indicating putative bacteriocin-like inhibitory substances (BLIS). The isolates survived intestinal conditions above the probiotic threshold, yet only SJC117 and SJC120 tolerated gastric acidity (pH 2.5, 1 h) with >5 log CFU/mL. Despite low hydrophobicity, strains showed good autoaggregation and pathogen coaggregation. All isolates produced exopolysaccharides (EPS) and angiotensin-converting enzyme (ACE) inhibitory peptides, whereas some exhibited moderate conjugated linoleic acid (CLA) production and glutamate decarboxylase (GAD) activity. L. paracasei SJC117 stood out by combining BLIS/antifungal activity, superior gastric tolerance, and an exceptional bioactive profile, making it a promising candidate for biopreservation and functional food applications that warrants further in vivo validation to confirm its efficacy and safety. Full article

Chagas disease, caused by Trypanosoma cruzi, remains a major public health problem in Latin America and an emerging global health concern due to population mobility. Although benznidazole and nifurtimox remain the only approved antiparasitic drugs, their limited efficacy in chronic infection, prolonged treatment regimens, frequent adverse effects, and variable activity across parasite strains highlight the need for new therapeutic strategies. In addition, the pathogenesis of chronic Chagas disease is driven not only by parasite persistence but also by immune-mediated tissue damage, particularly in chronic Chagas cardiomyopathy. In this review, we examine emerging therapeutic approaches that extend beyond conventional trypanocidal chemotherapy, with emphasis on natural products, antimicrobial peptides, and cell-based immunomodulatory strategies. Plant compounds and essential oils have shown antiparasitic activity through mechanisms including oxidative stress induction, membrane disruption, interference with sterol biosynthesis, and mitochondrial dysfunction, while some extracts also modulate host immune responses. Antimicrobial peptides display dual potential by directly damaging parasite membranes and organelles or by reshaping infection-associated inflammatory responses. In parallel, cell-based therapies such as mesenchymal stromal cells, tolerogenic dendritic cells, and bone marrow-derived cells have demonstrated promising cardioprotective and immunoregulatory effects in experimental chronic Chagas disease. Collectively, these approaches support a multitarget therapeutic framework in which parasite-directed and host-directed interventions may complement each other. Further mechanistic studies, standardization, and translational validation will be essential to advance these candidates toward clinically useful therapies for Chagas disease. Full article

The growing concern over antimicrobial resistance and the increasing demand for safer and more sustainable antimicrobial strategies have driven extensive research into peptide-based natural antimicrobials. This review focuses specifically on antimicrobial peptides (AMPs), bacteriocins and mycocins as peptide- or proteinaceous antimicrobial compounds with potential applications as active ingredients, biopreservatives and antimicrobial tools. These compounds exhibit activity against spoilage and pathogenic microorganisms and are increasingly being explored in food safety, agriculture, cosmetics, animal health and human healthcare. AMPs, bacteriocins and mycocins act through diverse and sometimes overlapping mechanisms, including membrane disruption, pore formation, inhibition of cell wall biosynthesis, interference with intracellular targets, induction of oxidative stress and modulation of host or microbial responses. These mechanisms support their potential use in food biopreservation, crop protection, biofungicide and biopesticide development, topical antimicrobial formulations, cosmetic preservation, antibiofilm strategies and adjunctive therapeutic approaches. Recent advances in encapsulation, peptide engineering, recombinant production, nanodelivery and combination strategies with conventional antibiotics, hurdle technologies or other natural antimicrobials have improved the stability, bioavailability and antimicrobial efficacy of these compounds in experimental systems. However, broader translation remains limited by several major challenges. These include proteolytic degradation, reduced stability in complex matrices, context-dependent antimicrobial activity, possible toxicity, resistance development, high production and purification costs, formulation difficulties, scale-up limitations and regulatory constraints. Further validation is also needed regarding safety, microbiome impact, environmental fate and performance under realistic food-preservation, agricultural, cosmetic and clinical conditions. This review summarises and compares the diversity, mechanisms, applications and translational challenges of AMPs, bacteriocins and mycocins across food safety, sustainable agriculture, cosmetics, animal health and healthcare. It also discusses the main challenges that must be addressed before broader translation, including resistance risk, stability, formulation, scale-up, safety assessment and regulatory approval. Full article

Porcine epidemic diarrhea virus (PEDV) imposes substantial economic losses on the global swine industry owing to its high pathogenicity and transmissibility. Although arginine (Arg) is known to support the integrity of intestinal barrier, it is not clear whether Arg can alleviate intestinal injury induced by PEDV. A total of 32 healthy 7-day-old piglets were randomly assigned to four groups (Control, Arg, PEDV, PEDV + Arg; eight replicates per group). From day 5, piglets in the Arg and PEDV + Arg groups were orally administered Arg at 400 mg/kg body weight until day 11; then, PEDV (1 × 10^5.5 TCID₅₀) was given orally for two PEDV-infected groups. On day 14, all piglets were slaughtered to obtain blood and intestine samples for further analysis. The results showed that PEDV infection significantly reduced T-SOD and CAT activities in plasma and intestine while elevating MPO levels. Arg supplementation restored T-SOD (plasma, duodenum, ileum), CAT (plasma, ileum), and GSH-Px (jejunum, ileum) activities and reduced MDA (jejunum) content in PEDV-infected piglets. Hematological analysis showed Arg alleviated PEDV-induced increases in MCV and RDW-SD, and significantly elevated MCHC. The real-time quantitative PCR analysis demonstrated that Arg further enhanced PEDV structural genes (M, N, S) expression in the duodenum, ileum, and colon. Concurrently, Arg significantly up-regulated interferon-stimulated genes (MX1, OASL, ISG15, IFITM3) in the ileum, IRF7 in the duodenum and colon, and IFN-β in the ileum. Arg also down-regulated the pro-inflammatory cytokines IL-6 and CXCL2 and the antimicrobial peptide REG3G in the colon, while up-regulating the tissue repair gene MMP13 in the ileum. In conclusion, oral Arg exhibits a unique dual role: it promotes PEDV replication to a certain extent while significantly enhancing antioxidant capacity, strengthening intestinal antiviral immunity, and attenuating intestinal inflammation. These findings highlight Arg’s role in promoting disease tolerance and offer a novel perspective for nutritional intervention strategies against PEDV infection. Full article

Polysaccharide–peptide conjugates are modular biomaterials that combine hydrated carbohydrate frameworks with peptide domains capable of mediating molecular recognition, degradability, antimicrobial activity, and biological signaling. In this review, we discuss how covalent, bioorthogonal, and enzymatic conjugation strategies regulate peptide density, orientation, accessibility, and stability within polysaccharide-based matrices. These chemical choices are analyzed in relation to network architecture, viscoelasticity, ligand presentation, degradation behavior, and cell–material interactions. Representative systems based on hyaluronic acid, alginate, chitosan, dextran, cellulose, and glycosaminoglycans are examined to illustrate how peptide functionalization can transform otherwise passive scaffolds into adhesive, degradable, antimicrobial, or therapeutically responsive platforms. We further highlight dynamic and enzyme-responsive materials, localized drug delivery systems, antimicrobial coatings, and antibiofilm interfaces as key biomedical applications of these conjugates. The review also addresses translational challenges associated with structural heterogeneity, stability, immunogenicity, sterilization, batch-to-batch reproducibility, and clinical feasibility. Taken together, the evidence discussed here indicates that the performance of polysaccharide–peptide conjugates depends on reproducible structure–function relationships linking conjugation chemistry, macromolecular architecture, and biological activity under application-relevant conditions. Full article