Despite remarkable progress in the fields of vaccinology and antiviral therapy, viral infections persist as a leading cause of morbidity and mortality worldwide. Therefore, it is crucial to identify new and effective antiviral drug candidates. Scorpion venoms are viewed as a rich source of structurally diverse and biologically active peptides, which may present opportunities for diagnostic, preventive, and therapeutic applications. This review intends to provide a contemporary and detailed analysis of scorpion-derived peptides, with a particular focus on their structural diversity, cytotoxic effects, antiviral properties, and mechanisms of action. Additionally, this paper highlights several potential fruitful areas for future studies. Current evidence indicates that scorpion-derived peptides are effective against a wide array of medically important viral pathogens such as chikungunya virus, dengue virus, enterovirus 71, hepatitis B virus (HBV), herpes simplex virus 1, human immunodeficiency virus 1, influenza A virus (IAV), severe acute respiratory syndrome coronavirus-2, and Zika virus. Nevertheless, the majority of these findings have been obtained from in vitro studies, whereas evidence from animal models remains limited and clinical evaluation in humans is currently unavailable. Available studies suggest that these peptides may act through diverse mechanisms of action, including direct virucidal activity, inhibition of viral entry, immune system modulation, reduction of virus-induced cytopathic effects, and suppression of viral gene expression. Emerging evidence also demonstrates the efficacy of certain scorpion-derived peptides in animal models of HBV, IAV, and Newcastle disease virus infection. Overall, such peptides appear to inaugurate new avenues for the treatment of viral infections.
Intestinal enteric inflammation can seriously harm animal health and lead to massive economic losses in livestock production. Probiotics have become a promising alternative to antibiotics for preventing and controlling enteritis. In this study, a novel lactic acid bacterium (LAB) was isolated from eagle feces and identified as Weissella confusa EG05 (W. confusa EG05), and its probiotic characteristics and protective effects on lipopolysaccharide (LPS)-induced enteritis in mice were evaluated. In vitro experiments showed that W. confusa EG05 has strong antimicrobial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), good tolerance to acidic and bile salt conditions, high auto-aggregation ability and surface hydrophobicity, and no hemolytic activity. Whole-genome analysis further confirmed its safety and probiotic potential by revealing genes involved in adhesion, immune regulation, and stress tolerance. In mouse experiments, pretreatment with W. confusa EG05 alleviated LPS-induced intestinal pathological damage, inhibited the secretion of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6), promoted the expression of anti-inflammatory cytokine IL-10, enhanced the activities of antioxidant enzymes, and up-regulated the expression of tight junction proteins (Occludin, ZO-1). In addition, W. confusa EG05 restored gut microbiota homeostasis disturbed by LPS, increasing the abundance of beneficial genera and decreasing harmful bacteria. Taken together, these results suggest that W. confusa EG05 can effectively prevent LPS-induced enteritis in mice by modulating the inflammatory response, enhancing antioxidant capacity, protecting the intestinal barrier and the reshaping gut microbiota. These results indicate that W. confusa EG05 exhibits prominent probiotic potential in mouse models, providing a strain resource for the future development of microecological preparations.
Probiotic-based strategies have gained increasing attention as potential interventions for obesity and metabolic disorders. Lactococcus lactis subsp. lactis CAB701 (CAB701), a cabbage-derived probiotic strain, has demonstrated anti-adipogenic activity in preclinical studies; however, its clinical efficacy has not been established. We conducted a single-centre, randomized, double-blind, placebo-controlled 12-week trial in 100 Korean adults with overweight or obesity (mean age 48.9 ± 13.9 years; body mass index (BMI) 25.8 ± 1.8 kg/m²; 19
This review examines the therapeutic potential of probiotics in alleviating colitis through animal model studies, with particular emphasis on elucidating their mechanisms of action. Growing evidence demonstrates that gut dysbiosis plays a significant role in colitis pathophysiology, and restoring gut homeostasis represents a promising treatment strategy. Recent findings reveal that intestinal homeostasis is regulated not only by microbial composition but also by host-mediated oxygen control, which critically influences intestinal epithelial energy metabolism in both healthy and dysbiotic states. Interventional animal studies demonstrate that probiotics and their metabolites maintain gut homeostasis through multiple mechanisms. These include enhancing intestinal barrier integrity, preserving mucosal barrier function, and suppressing NF-κB pathway activation. Probiotics also modulate inflammatory responses by reducing pro-inflammatory cytokines such as TNF-α, IL-1β, IL-18, IL-6, and IL-17, while increasing anti-inflammatory cytokines like IL-10 and IL-13. Furthermore, they regulate macrophage polarization by downregulating M1 (pro-inflammatory) and upregulating M2 (anti-inflammatory) phenotypes. Additionally, probiotics ameliorate oxidative stress by boosting antioxidant enzyme activity (SOD, CAT, GPx, GST), increasing glutathione (GSH) levels, and decreasing MPO and MDA concentrations.
Lactic acid bacteria (LAB) play a key role in milk fermentation by producing a wide range of metabolites that influence the nutritional, functional, and health-promoting properties of fermented dairy products. The present study aimed to characterize the volatile metabolite profile of LAB-fermented cow milk obtained from different cow breeds using gas chromatography-mass spectrometry (GC-MS) and to identify metabolites potentially associated with its biological activities. Additionally, the antimicrobial activity of fermented milk was evaluated against Bacillus subtilis, Escherichia coli, Pseudomonas fluorescens, and Micrococcus luteus using the agar well diffusion method, while α-amylase inhibitory activity was determined using an in vitro assay. The antibacterial and α-amylase inhibitory activities of fermented milk samples were significantly higher (p < 0.05) than unfermented milk samples. Following ultrafiltration using 3 and 10 kDa membranes, the 3 kDa retentate from the Sahiwal cow milk (SCM) fermented milk sample exhibited the highest antimicrobial activity (inhibition zone: 1.78 cm), whereas the 10 kDa filtrate from the Holstein Friesian cow (HFCM) fermented milk sample showed the highest α-amylase inhibitory activity (51.90
The aim of this study was to isolate, molecularly identify, and comprehensively evaluate the probiotic potential of native Bacillus strains from the soil of Isfahan province, Iran. Using the thermal enrichment method, 23 Gram-positive spore-forming strains were isolated. Following preliminary safety screening, three superior strains (NF16, NF20, and NF24) were selected based on the absence of hemolytic activity (γ-hemolysis), lack of lecithinase production, and absence of enterotoxin genes (hbl and nhe). The strains were identified as Bacillus zhangzhouensis NF16, Bacillus pumilus NF20, and Bacillus safensis NF24 through 16 S rRNA genes sequence. Their 16 S rRNA gene sequences were deposited in the NCBI GenBank database under the accession numbers PX930946, PX930921, and PX930970, respectively. All three strains demonstrated excellent tolerance to simulated gastrointestinal conditions, the survival rates of the three tested strains ranged from 48.59
Viral, bacterial, and parasitic diseases in food-producing and companion animals are permanent problems for humankind. Research to solve this concern includes those based on modulation of the immune system, such as probiotic supplementation and vaccination. Vaccines are a cheap alternative to prevent and control diseases, while probiotics provide several health benefits to the host, including immunostimulation. Research on unified strategies has been scarcely explored, but the current results evidence that probiotics can serve as potentiators of vaccines. Yeast and bacterial probiotic supplementation, mono- or multi-species and before or after vaccination, among other assessments, in ruminants, equines, swine, poultry, fish, and dogs, against bacterial, viral and/or parasitic infections has revealed increased immune responses and, in a few studies, protective outcomes. Therefore, this review aimed to describe those scientific findings and discuss their limitations and implications for the use of probiotics as vaccine enhancers in veterinary species. Through the modulation of innate and adaptive immune responses, probiotic usage may also expand opportunities for the development of potential vaccine enhancers in veterinary medicine.
Dietary intake of oxidized oil is increasingly recognized as a key contributor to metabolic dysfunction. In this study, we evaluated the protective effects of Lactobacillus fermentum MCC2760 (LF) against oxidized oil-induced metabolic dysfunction across two generations in rats. Female Wistar rats were fed AIN-76 diets containing native or thermally oxidized sunflower oil (SFO) and canola oil (CNO), with or without LF supplementation (10⁹ CFU/day), and the F2 generation was maintained on corresponding diets. Biochemical parameters including lipid profile, oxidative stress (OS) markers (lipid peroxides, protein carbonyls), antioxidant defense enzymes (catalase, SOD, GR, GPx, GST), inflammatory mediators (PGE2, LTB4, TNF-α, MCP-1, IL-1β, IL-6), transcription factors (NF-κB, Nrf2), organ function enzymes (SGOT, SGPT, CK-MB, CK-NAC, ALP) and fecal microbiome were assessed. Consumption of oxidized oils, irrespective of fatty acid composition, significantly disrupted lipid homeostasis, increased OS, reduced antioxidant enzyme activities and Nrf2 activity, and enhanced NF-κB activity, leading to elevated inflammatory mediators. Oxidized oil intake also increased serum markers of hepatic and cardiac injury, and induced gut dysbiosis. However, daily administration of LF significantly attenuated these metabolic disturbances by improving lipid homeostasis, antioxidant defenses, and inflammatory balance, NF-κB/Nrf2 activities, and gut microbial composition. These protective effects were consistently observed in both F1-mothers and F2 offspring, supporting metabolic resilience across generations. Overall, these findings support the potential of probiotic LF as a functional dietary strategy for mitigating oxidized oil-induced metabolic dysfunction by improving lipid homeostasis, modulating NF-κB/Nrf2 activities, and promoting gut microbial balance, with findings consistent with the involvement of the gut-liver axis.
Given the similarities of action mechanism between amyloidogenic peptides (e.g. Aβ) and antimicrobial peptides (AMPs), we rationally engineered an amyloidogenic Aβ peptide to improve its antimicrobial activity: the aggregation-prone fragment was reverse-repeated to increase antimicrobial activity; poly-arginine (R) was flanked to both ends of the repeated fragments to enhance membrane interaction and inhibit amyloidogenesis; a β-turn fragment (DPDG/YNGK) was inserted between the repeated fragments to inhibit amyloidogenesis. Antimicrobial assays demonstrated that the designed peptides exhibited significantly enhanced antimicrobial activity. Among the designed peptides, Aβ-6R-YNGK, Aβ-6R-YNGK-r, Aβ-10R-YNGK, and Aβ-10R-YNGK-r exhibited potent antimicrobial activity, particularly against Staphylococcus epidermidis with MICs of 5, 5, 5, and 1 µM, respectively. Moreover, at 20 µM, these peptides showed significant anticancer activity and low cytotoxicity, reducing U937 human lymphoma cell viability to below 30
Peptide drugs are vital for treating intractable diseases, yet traditional discovery is limited by huge sequence space and poor pharmacokinetics. Generative Adversarial Networks (GANs) and related variants (CGAN, WGAN-GP, MPOGAN) are increasingly used as auxiliary computational tools for peptide drug discovery, primarily for de novo sequence exploration and multi-property optimization of antimicrobial, antiviral and anticancer peptides. Reported gains in predicted activity or novelty are study-specific and frequently remain limited to in silico evaluation or early in vitro assays. This review summarizes GAN architectures, database foundations, and diverse applications; discusses major limitations, including multi-label data scarcity and property trade-offs; and proposes future directions, including LLM-assisted annotation and closed-loop AI-experimental platforms. It aims to organize current evidence for AI-driven peptide design, emphasize methodological and translational limitations, and outline a realistic pathway toward clinical translation.
Excessive ultraviolet (UV) exposure induces oxidative stress and disrupts normal melanogenesis, leading to pigmentation disorders and skin damage. Probiotic-derived postbiotics, including extracellular vesicles (EVs), have recently emerged as promising bioactive agents for skin health. Therefore, this study aimed to investigate the anti-melanogenic and skin-protective effects of the cell-free supernatant (CFS), cell extract (CE), and EV-enriched fraction derived from Limosilactobacillus fermentum JNU532. In B16F10 melanocytes, both the CFS and CE significantly reduced melanin content and intracellular tyrosinase (TYR) activity in a dose-dependent manner, accompanied by downregulation of melanogenesis-related proteins (TYR, TRP-1, and TRP-2) and suppression of cyclic adenosine monophosphate signaling. In a UVB-induced hairless mouse model, topical application of the CFS and CE markedly decreased melanin accumulation, preserved epidermal structure, and prevented collagen loss. Notably, the EV-enriched fraction showed relatively stronger anti-melanogenic activity than CFS under the tested conditions, showing greater inhibition of melanin synthesis, intracellular TYR activity, and melanogenesis-related gene expression, including TYR, TRP-1, TRP-2, and MITF. Proteomic profiling revealed multiple proteins commonly identified in bacterial EVs, including membrane-associated and transporter-related proteins, supporting the vesicular characteristics of the EV-enriched fraction. These findings indicate that JNU532-derived CFS, CE, and EV-enriched fractions exhibit anti-melanogenic and skin-protective effects, with enhanced activity observed in the EV-enriched fraction under the tested conditions.
Elizabethkingia anophelis is a multidrug-resistant opportunistic pathogen associated with severe neonatal meningitis, sepsis, and hospital outbreaks, with high mortality rates and limited treatment options. In this study, a hybrid multi-epitope vaccine (MEV) was designed using an extensive immunoinformatics approach targeting four key outer membrane and secretion-associated proteins. Highly antigenic B-cell and T-cell (MHC-I and MHC-II) epitopes were predicted, rigorously screened for antigenicity, allergenicity, toxicity, and cytokine induction potential, and selected based on binding affinity and population coverage. The final MEV construct incorporated eight MHC-I, eight MHC-II, and eight B-cell epitopes linked with appropriate linkers, adjuvanted with Human Beta Defensin-3, and tagged with a 6 × His sequence. Population coverage analysis revealed 99.38
Lactiplantibacillus plantarum is a metabolically versatile lactic acid bacterium found in fermented foods and the human gastrointestinal tract. Its relatively large genome (3.0–3.6 Mb) features an open pan-genome with 1,436–2,100 core genes and over 13,000 cloud genes, enabling remarkable adaptation to diverse environments. This species encodes a diverse repertoire of CAZymes that degrade plant polysaccharides and host glycans, yielding short-chain fatty acids that modulate epithelial barrier integrity, host metabolism, and immune signaling. Pattern-recognition receptors (PRRs, including TLR2, TLR9, and NOD2) detect L. plantarum at the host interface, primarily through cell-surface molecules such as lipoteichoic acids, peptidoglycan, and exopolysaccharides. These interactions can influence NF-κB signaling, leading to either inflammatory or regulatory responses, depending on the specific strain. Certain strains also possess the glutamate decarboxylase system (GadB/GadC), which transforms dietary glutamate into gamma-aminobutyric acid (GABA), linking L. plantarum to the biology of the gut-brain axis. Despite substantial mechanistic evidence, clinical outcomes are inconsistent due to the significant variability among strains, marked differences in host microbiomes, and the absence of predictive multiomic markers for colonization and efficacy. This review consolidates current insights on genome organization, metabolic characteristics, and mechanisms of host interaction, with a specific focus on the challenges that continue to hinder the advancement of L. plantarum as a precision biotherapeutic.
Intestinal mucosal barrier dysfunction is a critical driver of various gastrointestinal disorders, typically manifesting as physicochemical barrier disruption, immune dysregulation, and microbial dysbiosis. Harnessing the potent antioxidant properties and high intestinal bioavailability of phytoene, alongside the suitability of Saccharomyces cerevisiae as a food-grade expression host, we evaluated the efficacy of engineered phytoene-producing S. cerevisiae (PSc) in attenuating cyclophosphamide (CP)-induced jejunal mucosal damage in mice. Single-dose oral retention assays revealed that PSc preserved viability during gastric transit and transiently colonized the intestine for over 24 h. Dietary supplementation with PSc effectively mitigated CP-induced jejunal injury and reversed the pathological atrophy in lymphoid organs, specifically the spleen and thymus. Mechanistically, PSc restored the mucus barrier by augmenting goblet cell counts and MUC2 expression, reinforced epithelial integrity by upregulating tight junction proteins, and fortified the immunological barrier by modulating the secretion of sIgA and cytokines (e.g., IL-1β, IL-6, TNF-α, and TGF-β3). Furthermore, PSc remodeled both gut bacterial and fungal communities, enriching beneficial taxa such as Muribaculaceae, Lachnospiraceae, and Kazachstania while suppressing pathogenic microbes, thereby restoring microbial homeostasis and facilitating mucosal repair. In conclusion, this study demonstrates that PSc ameliorated CP-induced intestinal injury by restoring multi-layered barrier functions, establishing a robust rationale for its development as a novel probiotic and functional food supplement for managing chemotherapy-induced intestinal complications.
Bacterial infections pose a significant threat to human health, and the prudent use of antibiotics remains a critical component of disease treatment and control. The increase in drug resistance of pathogenic bacteria poses a huge challenge to the world. Probiotics have become a promising approach to combating pathogenic bacterial infections. In this research, we found that the SKS1-KO Saccharomyces cerevisiae showed effective antibacterial activity against common clinical pathogenic bacteria in vitro, which has been confirmed through the determination of the minimum inhibitory concentration (MIC), growth curve analysis, inhibitory spectrum analysis and co-culture experiments. This strain has remarkable self-aggregation and co-aggregation characteristics. In addition, we used Galleria mellonella infected with Escherichia coli and Staphylococcus aureus as a model to evaluate the antibacterial activity of the SKS1-KO strain in vivo. We found that treatment with this strain significantly prolonged the survival time of the G. mellonella. Mass spectrometric quantification revealed significantly elevated levels of acetic acid, propionic acid, isobutyric acid, isovaleric acid, and hexanoic acid in the SKS1-KO cell-free supernatant (CFS) compared with the parental BY4743 strain. Exogenous supplementation of these fatty acids to BY4743 CFS enhanced its antibacterial activity, confirming that the increased accumulation of multiple fatty acids contributes to the enhanced phenotype. The SKS1-KO strain shows potential as a probiotic candidate for further preclinical development.
Otitis media prevention remains challenging due to antibiotic resistance and frequent recurrence. This review proposes a novel strategy based on probiotic modulation of the Eustachian tube microenvironment. The approach leverages a dual-mechanism whereby probiotics secrete biosurfactants that contribute to the restoration of physiological surface tension and mucus flow, while simultaneously producing antimicrobial peptides that directly eliminate pathogens and suppress inflammatory responses. This synergistic action may not only facilitates sustainable colonization by beneficial bacteria but also disrupts the cycle of biofilm formation and functional impairment in the Eustachian tube. Experimental evidence and clinical observations indicate that this probiotic-based intervention correlates with significantly reduced incidence of otitis media and decreased recurrence rates. Future translation into clinical practice will require further development of optimized strain-specific formulations and effective delivery systems to fully realize this therapeutic approach. This review aims to critically evaluate current evidence supporting probiotic-mediated modulation of the Eustachian tube microenvironment, with particular emphasis on the complementary roles of biosurfactants and antimicrobial peptides in preventing otitis media, while highlighting the current limitations and future translational challenges. These findings highlight the potential of probiotic-mediated modulation of the Eustachian tube environment as a promising preventive strategy.
Assisted reproductive technologies (ART) have transformed infertility treatment over recent decades, yet success rates remain inconsistent. Beyond the established embryological and hormonal determinants, emerging research identifies the human microbiome—particularly gut and reproductive tract communities—as a critical regulator of reproductive efficiency. The gut microbiota influences endocrine balance, metabolic signaling, and immune homeostasis, all of which have a direct impact on oocyte maturation, embryo viability, and endometrial receptivity. Dysbiosis, characterized by the depletion of beneficial lactobacilli and an increase in pro-inflammatory bacterial taxa, has been associated with oxidative stress, reduced oocyte competence, and implantation failure. In contrast, a balanced microbiota supports follicular health and hormonal coordination. Prebiotic and probiotic interventions may enhance reproductive outcomes through several complementary mechanisms. By restoring a Lactobacillus-dominant microbial profile, they help stabilize the reproductive tract ecosystem, reinforce epithelial and immune barrier function, and limit the overgrowth of potentially pathogenic species. These changes reduce local inflammation and oxidative stress while promoting the secretion of antimicrobial peptides and bacteriocins that maintain tissue integrity. Collectively, these microbiome-mediated effects can contribute to improved follicular fluid homeostasis, enhanced oocyte competence, better early embryo development, and ultimately higher ART success rates. In conclusion, modulation of the gut-reproductive axis through targeted probiotic or prebiotic therapy represents a promising biological adjunct to assisted reproduction. Further mechanistic studies and large-scale randomized trials are warranted to validate its clinical applicability and optimize therapeutic regimens.
Acrylamide (AA) is a food-derived contaminant linked to oxidative stress and genotoxicity in intestinal epithelial cells. This study had two objectives: (i) to evaluate the protective effects of cell-free supernatants from Lacticaseibacillus rhamnosus 0997 and Kluyveromyces lactis 0028 against AA-induced damage in Caco-2 cells, and (ii) to investigate AA-induced changes in the surface and functional properties of selected lactic acid bacteria and yeast strains. Cell-free supernatants significantly enhanced DNA repair, reduced genotoxicity, and decreased intracellular reactive oxygen species in Caco-2 cells in a concentration- and AA-dose-dependent manner (p < 0.05). L. rhamnosus 0997 showed stronger cytoprotection at higher AA concentrations, whereas K. lactis 0028 was more effective under lower AA exposure. Independently, AA altered auto-aggregation, biofilm formation, hydrophobicity, adhesion, and zeta potential of the tested microbial strains in a strain-specific manner. These findings demonstrate the cytoprotective potential of microbial cell-free supernatants against AA-induced cellular damage and characterize the effects of AA on selected microbial surface properties.
Antimicrobial peptides (AMPs) are increasingly recognized as regulators of immune cell function, yet whether they engage nuclear regulatory circuits to control macrophage activation remains unclear. Here, we report that the bovine cathelicidin BSN-37 promotes macrophage immune activation through a regulatory mechanism associated with the nuclear circRNA circBptf and the RNA-binding protein Rbm14. Transcriptomic profiling revealed that BSN-37 markedly remodels the circRNA landscape and consistently suppresses circBptf, a circular RNA derived from the chromatin-regulatory Bptf locus. circBptf is a stable nuclear RNA that functions as a negative regulator of macrophage activation, limiting cytokine production and antigen-presentation-related molecules. Mechanistically, circBptf physically associates with the nuclear RNA-binding protein Rbm14, a transcriptional co-regulator linked to immune gene expression. Functional perturbation analyses indicate that circBptf overexpression suppresses macrophage activation, whereas Rbm14 promotes the expression of cytokines and antigen-presentation-related molecules. Functional rescue experiments further support a circBptf–Rbm14-associated regulatory module involved in BSN-37-induced macrophage activation. Together, these findings support a nuclear circRNA–RBP-associated regulatory module linking an antimicrobial peptide to circRNA-mediated control of transcription and identify circBptf as a negative regulatory component of macrophage activation. This work expands the understanding of AMP-mediated immunoregulation by revealing how noncoding RNA–protein interactions contribute to coordinated immune gene expression.
C-phycocyanin (C-PC) is a promising anti-aging nutraceutical due to its antioxidant and anti-inflammatory properties; however, its instability under acidic conditions limits its efficacy, necessitating advanced formulation strategies. This study evaluated the anti-aging potential of novel enteric C-PC nanoparticles (NPs) co-delivered with Pediococcus pentosaceus in a D-galactose-induced aging model in male Wistar rats. C-PC was extracted from microalgal biomass and encapsulated into Eudragit® S100 nanoparticles. Particle size, encapsulation efficiency, zeta potential, pH-responsive release, and morphology were characterized. Aging was induced in male Wistar rats using D-galactose. Oxidative stress markers, neurotransmitters, acetylcholine metabolism, behavioral performance, and brain histopathology were assessed following treatment with C-PC nanoparticles with or without probiotic co-supplementation. C-PC was extracted from 2.5 g dry biomass with a yield of 31.02
