Search Results (2,942)

Plant immune genes are traditionally classified as resistance genes, susceptibility genes, or positive/negative regulators of defense. However, this framework does not fully explain a subset of immune-associated genes that display paradoxical disease phenotypes, in which genetic disruption enhances resistance despite the normal involvement of these genes in defense-related processes. GSL5/PMR4 is a representative example. As a pathogen-induced callose synthase, GSL5 contributes to papillary callose deposition and structural defense. Paradoxically, loss of GSL5 confers resistance to powdery mildew through salicylic acid- and N-hydroxypipecolic acid-associated pathways, as well as broad-spectrum resistance to Plasmodiophora brassicae through jasmonic acid-dependent immunity. Here, we refer to such genes as dual-state immune regulators, whose functional presence and genetic disruption promote resistance through distinct immune states. Similar regulatory patterns have been reported in several immune-related processes, including MAPK signaling, calcium influx, membrane trafficking, and receptor-proximal immune signaling. Representative examples include the MEKK1–MKK1/MKK2–MPK4 module, CNGC2/CNGC4, EXO70B1 and BIK1. This review uses GSL5 as a central example to discuss paradoxical immune phenotypes and dual-state immune regulators in plants, focusing on their biological features, potential mechanisms, and implications for resistance breeding. Full article

Pseudomonas aeruginosa, an opportunistic pathogen, is a major threat to hospital infection control and global public health due to its strong environmental adaptability, complex virulence systems, efficient biofilm formation capability, and widespread multidrug resistance. Traditional single-target antibiotics are often inadequate for clinical treatment. The research into Plant-Derived Bioactive Compounds for combating P. aeruginosa infections is reviewed, highlighting their advantages (many of which are extensively studied in Traditional Chinese Medicine) over conventional antibiotics. The antimicrobial mechanisms of these compounds include the inhibition of bacterial quorum sensing (QS) systems to suppress virulence factor expression rather than direct anti-bactericidal effects, delaying the development of resistance. The abundant natural medicinal plants and their diverse chemical structures provide ample material for active compound screening to identify unique chemical compositions with specific binding to pathogen targets. Plant-Derived Bioactive Compounds exhibit excellent safety profiles, targeting bacterial-specific pathways or host immune regulation, resulting in minimal off-target toxicity. Plant-Derived Bioactive Compounds exert anti-P. aeruginosa effects via inhibition of QS systems to reduce pathogenicity by disrupting intercellular signaling, suppressing biofilm formation/maturity to overcome biofilm-associated resistance, directly interacting with bacterial structure. Plant-Derived Bioactive Compounds are promising treatments for drug-resistant P. aeruginosa infections, providing lead compounds for novel anti-infective drug development. Full article

Chemical agents have long been used to control plant diseases, but their effects on the environment and lack of alignment with sustainable development goals are making them gradually unsuitable. One trend in green agriculture is the use of Bacillus species for the biocontrol of plant diseases. Due to their vast metabolic and genetic diversity, Bacillus spp. can contribute significantly to the soil ecosystem, while also enhancing plant resilience to biotic and abiotic stresses. Bacillus spp. are widely used in the agrobiotech industry due to their multi-functional versatility and are well-known for protecting plants from numerous plant diseases. In this review, we discussed the diversity and functions of antimicrobial compounds (AMCs) produced by Bacillus spp., along with their roles in plant growth promotion (PGP), and immunity. Furthermore, we highlighted the potential of Bacillus spp. as biopesticides in host plants, ways to enhance their biocontrol efficacy, and also addressed their possibility to cause disease in host plants. Considering the beneficial impacts of Bacillus spp. on PGP and pathogen biocontrol and their disease-causing capability, we discussed the possible solutions for a safe development of Bacillus-based biocontrol agent (BCA). Collectively, these insights can guide the selection of Bacillus strains with broad-spectrum or target-specific activity against pathogens, ensuring minimal adverse effects on the host. Full article

N-hydroxypipecolic acid (NHP) is a key mobile signal in systemic acquired resistance in plants, and its glycosylation has been proposed to regulate immune signaling. Previous studies have demonstrated that the UDP-glycosyltransferase UGT76B1, known as an SA glycosyltransferase in Arabidopsis thaliana, also catalyzes NHP glycosylation. In this study, we re-evaluated NHP glycosylation activity of UGT76B1 using an in vitro enzyme-coupled fluorescence assay that quantitatively detects UDP released during UDP-sugar-dependent glycosylation. Unexpectedly, our biochemical analyses demonstrated that UGT76B1 lacks genuine glycosylation activity toward NHP under the in vitro assay conditions tested, although this system clearly detected UGT76B1 activity toward salicylic acid (SA), as well as the activities of UGT74F1 and UGT72B1 toward SA and hydroquinone, respectively. To explore potential UGTs responsible for NHP glycosylation, we evaluated the enzymatic activities of 41 UGT candidates successfully expressed in Escherichia coli, which are selected based on transcriptomic responses to tenoxicam treatment, molecular docking simulations using AlphaFold3/AutoDock Vina, phylogenetic criteria, and previous reports. Within this selected and successfully expressed UGT panel, none exhibited authentic NHP glycosylation activity, although this does not preclude the possibility that other members of the Arabidopsis UGT family possess NHP glycosyltransferase activity. Our findings challenge the prevailing view that UGT76B1 is the primary glycosyltransferase for NHP in A. thaliana and indicate that NHP metabolism may rely on undiscovered non-canonical enzymes or distinct metabolic pathways that warrant further investigation. Full article

Astragalus membranaceus, a medicinal plant used in traditional Chinese medicine for centuries, has attracted growing scientific attention for its potential anti-aging and anticancer properties, particularly for skin and bone health. Its key bioactive compounds like astragalosides, cycloastragenol, and its commercial derivative TA-65, have been associated with telomerase activation and telomere maintenance, suggesting a possible role in modulating cellular senescence and tissue repair processes. In addition to the claimed telomere maintenance, A. membranaceus exhibits antioxidant, anti-inflammatory, and DNA-protective activities, properties that contribute to its anti-aging effects. Emerging evidence also suggests that telomerase modulation by A. membranaceus influences cancer cell dynamics, either suppressing tumor progression through immune regulation and apoptosis induction or, in some contexts, potentially promoting tumor growth. This duality highlights the importance of dose, formulation, and targeted application. Clinically, TA-65 has been reported to improve vascular health, bone mineral density, and skin elasticity in aging individuals. Preclinical studies further support its protective effects against osteoporotic bone loss and photoaging-induced dermal degeneration. This review summarizes the phytochemical composition of A. membranaceus and critically evaluates the mechanistic and therapeutic evidence underlying its anti-aging and anticancer actions on skin and bone tissues. It also discusses the pharmacokinetic properties of A. membranaceus, including its absorption, bioavailability, and safety profile. The integration of A. membranaceus into evidence-based senile therapeutic strategies holds promise, but further mechanistic and clinical studies are required to optimize its safety and efficacy. Full article

Neuroinflammation, mediated by microglia and astrocytes, is an abnormal immune reaction in central nervous system (CNS) disorders. Stimulation of TRPV1 has been found to enhance microglial activation, resulting in a pro-inflammatory response. Natural anthraquinones such as physcion and rhein are commonly found in rhubarb, a medicinal plant recognized for its dual role in culinary and therapeutic applications. The therapeutic potential and mechanisms of these anthraquinones remain largely unexplored. This research aims to examine how anthraquinones protect against neuroinflammation and delineate the underlying mechanisms in lipopolysaccharide (LPS)-mediated cellular and zebrafish models. Among the representative anthraquinone analogs, physcion and rhein showed potent functional inhibitory activity against the TRPV1 channel. The production of nitric oxide (NO) and secretion of pro-inflammatory factors triggered by LPS were significantly reduced in BV-2 cells through regulation of iNOS, IL-6, IL-1β, and TNF-α mRNA expression. Moreover, physcion and rhein inhibited calcium influx and exerted anti-neuroinflammatory effects, which were closely associated with the suppression of Ca²⁺/CAMKK2/AKT and the PI3K/AKT-mediated NF-κB activation pathways. Furthermore, physcion and rhein reduced LPS-driven neutrophil recruitment to the brain and ameliorated locomotor deficits in zebrafish larvae, with the restoration of IL-1β, IL-6, and TNF-α transcript levels to baseline. In conclusion, natural-derived anthraquinones from rhubarb, physcion and rhein, acted as functional inhibitors of TRPV1-mediated calcium dynamics and significantly reduced LPS-mediated neuroinflammation in microglial cells and zebrafish larvae, suggesting promise as therapeutics for neurological disorders. Full article

Pathogenesis-related 1 (PR1) proteins are important components of plant defense and stress responses and also serve as precursors of CAP-derived peptides (CAPE), a class of small bioactive peptides involved in immune and stress signaling. Despite their potential biological significance, CAPE-producing PR1 genes have not been systematically characterized in tobacco (Nicotiana tabacum). In this study, a genome-wide analysis identified 17 CAPE-producing PR1 genes, designated NtCAPE1 to NtCAPE17, in the tobacco genome. These genes encode proteins containing conserved CAP domains and N-terminal signal peptides, with predicted hydrophilic properties and mainly vacuolar localization, indicating conserved structural features within the family. Phylogenetic analysis, gene structure organization, conserved motif profiling, chromosomal distribution, and synteny analyses revealed both evolutionary conservation and duplication-driven diversification of the NtCAPE family. Promoter cis-element analysis showed enrichment of regulatory elements associated with phytohormone signaling, development, and stress responses. Public transcriptomic datasets revealed dynamic and gene-specific expression patterns under water-deficit and salinity stress, and qRT-PCR analysis further confirmed the stress-responsive expression of selected NtCAPE genes. Functional assays using synthetic mature peptides showed that NtCAPE9 and NtCAPE17 alleviated salinity stress- and osmotic stress-induced leaf yellowing, improved chlorophyll retention, suppressed senescence-associated responses, reduced H₂O₂ accumulation and POD activity, modulated stress-responsive gene expression, and promoted seed germination under salinity and osmotic stress, respectively. These results provide a comprehensive characterization of CAPE-producing PR1 genes in tobacco and identify NtCAPE9 and NtCAPE17 as candidate stress-associated peptides with exogenous activity under salinity and osmotic stress conditions. Full article

Necrosis- and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs) are conserved microbial proteins that contain immunogenic patterns capable of activating plant pattern-triggered immunity (PTI). NLP patterns from Sclerotinia sclerotiorum (SsNLPs), a destructive necrotrophic fungal pathogen with a broad host range, have been identified, and their roles in PTI have been revealed. Nevertheless, the molecular mechanisms by which SsNLPs stimulate plant immunity remain largely unknown. In this study, we phylogenetically characterized SsNLPs and demonstrated the involvement of the phytocytokine receptor-like kinases PEPRs in SsNLP1-triggered immunity. SsNLPs contained the NPP1 domain and GHRHDWE motif and were phylogenetically closely associated with Botrytis cinerea NLPs. SsNLP1 treatment strongly induced the expression of PEPR genes. Further genetic analyses using Arabidopsis wild-type, pepr1 pepr2 double mutant, and PEPR1 overexpression lines showed that SsNLP1 elicited diverse immune responses, including reactive oxygen species (ROS) accumulation and defense gene activation, and induced plant resistance to S. sclerotiorum. Notably, the induced plant resistance and immune responses were strengthened in PEPR1 overexpression lines and significantly reduced in the pepr1 pepr2 mutant, indicating a positive role of PEPR signaling in SsNLP1-triggered immunity. Overall, our results revealed that phytocytokine PEPR1 signaling amplifies PAMP SsNLP1-triggered immunity, thereby enhancing resistance against S. sclerotiorum. Our findings provide an example of the coordination between PAMP- and phytocytokine-triggered immunity for robust resistance to a necrotrophic pathogen. Full article

Plant polysaccharides, such as Astragalus polysaccharide (APS) and Glycyrrhiza polysaccharide (GPS), have potential as functional feed additives. This study investigated the effects of dietary APS and GPS on growth-related traits, serum biochemical and immune indices, antioxidant capacity, intestinal health, and microbial diversity in early-weaned squabs. A total of 192 15-day-old Silver King squabs were randomly divided into four groups: the control group (CK), the 800 mg/kg APS group, the 450 mg/kg GPS group, and the APS + GPS combination group (AG group), with 12 replicates per group and 4 squabs per replicate. The experiment lasted for 28 days. The results showed that final body weight tended to be higher in the APS, GPS, and AG groups, whereas breast width and breast depth were significantly increased in the GPS and AG groups (p < 0.01). The GPS and AG groups exhibited increased serum immunoglobulin A (IgA; p < 0.05) and immunoglobulin G (IgG; p < 0.01) levels, as well as reduced levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α; p < 0.01). All treatments increased serum total antioxidant capacity (T-AOC; p < 0.01), while the AG group reduced malondialdehyde (MDA) levels and increased total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities (p < 0.01). Duodenal and jejunal T-AOC increased in all treatment groups (p < 0.01), and APS and AG increased ileal T-AOC (p < 0.01). However, intestinal MDA concentrations increased in several segments, indicating a complex and segment-specific oxidative response. The AG group also increased jejunal lipase activities (p < 0.05). Microbiome analysis suggested that Helicobacter was correlated with immune-related indicators, while Lactobacillus was identified as an important core genus in the microbial co-occurrence network. These findings suggest that dietary APS and GPS may regulate immune function, oxidative–antioxidant responses, intestinal function, and gut microbial composition, thereby supporting physiological adaptation in early-weaned squabs. Full article

In commercial pig production systems, early weaning imposes abrupt nutritional, environmental and social challenges before full gastrointestinal maturation has occurred, increasing susceptibility to post-weaning diarrhoea (PWD) and impaired growth performance. Although enterotoxigenic Escherichia coli (ETEC) is frequently implicated in PWD, pathogen presence alone does not adequately explain variation in disease expression among pigs and production systems. Increasing evidence indicates that gastrointestinal stability following weaning is determined by interactions among digestive capacity, substrate flow, microbial metabolism, epithelial integrity and host immune responses. In this review, substrate flow refers to the quantity, composition and regional distribution of undigested dietary and endogenous substrates moving through the gastrointestinal tract (GIT) and becoming available for microbial fermentation. The review proposes substrate flow as the central mechanistic interface linking digestive physiology with microbial metabolic activity during the post-weaning transition. Commercial weaning frequently occurs before complete adaptation to cereal- and plant-based diets has developed. Reduced feed intake, elevated gastric pH, incomplete pancreatic adaptation and reduced brush-border enzyme activity impair nutrient digestion during this transition, increasing nutrient overflow to the distal intestine. Under these conditions, microbial metabolism shifts from predominantly saccharolytic fermentation towards proteolytic pathways associated with production of ammonia, phenols, indoles and branched-chain fatty acids. These metabolites impair epithelial integrity, alter luminal conditions and favour proliferation of opportunistic bacteria. Conversely, effective digestion supports saccharolytic fermentation, short-chain fatty acid production, epithelial integrity and microbial stability. Microbial dysbiosis is therefore more accurately interpreted as a metabolic consequence of altered substrate availability and fermentation dynamics rather than solely as a compositional imbalance of bacterial taxa. By integrating digestive physiology, microbial ecology and nutritional management, the substrate-flow concept provides a mechanistic framework for development of more biologically coherent nutritional strategies aimed at improving gastrointestinal resilience and reducing antimicrobial reliance in modern pig production systems. Full article

Antimicrobial resistance (AMR) is one of the most serious threats to global public health, driven in part by extensive antibiotic use in food-producing animals. The poultry industry, a major contributor to the global animal protein supply, has depended on antibiotics for growth promotion and disease control, thereby contributing to the emergence and dissemination of AMR zoonotic bacteria. This review synthesizes current evidence on the potential of phytochemicals (PCs), plant-derived bioactive compounds, as sustainable non-antibiotic alternatives for controlling bacterial foodborne pathogens in poultry. Relevant literature including in vitro and in vivo studies assessing PCs against major poultry-associated zoonotic bacteria, including Salmonella enterica, Campylobacter spp., Clostridium perfringens, Listeria monocytogenes, and pathogenic Escherichia coli, is examined. Evidence indicates that PCs exert antimicrobial and anti-virulence effects through mechanisms like bacterial membrane disruption, inhibition of quorum sensing and virulence gene expression, modulation of gut microbiota, and enhancement of host immune responses. In vivo studies demonstrate reductions in pathogen colonization and improvements in gut health and performance metrics in poultry. Despite these promising findings, challenges remain in bioavailability, dose optimization, standardization, and regulatory approval. Overall, PCs represent a promising component of integrated antimicrobial stewardship strategies in poultry production, with significant implications for mitigating zoonotic AMR transmission. Full article

Food allergy (FA) is an increasing public health concern, highlighting the urgent need for safe, bioactive-based preventive strategies. This study evaluated genistein, a plant-derived isoflavone, in an ovalbumin (OVA)-induced murine FA model. Genistein was administered before sensitization and throughout allergy induction. Clinical symptoms, rectal temperature, diarrhea, OVA-specific antibodies, mast cell responses, intestinal barrier markers, gut microbiota, short-chain fatty acids (SCFAs), and fecal metabolites were assessed using immunological, histological, microbiome, and metabolomic analyses. Genistein pretreatment prevented OVA-induced clinical symptom scores, rectal temperature decline, diarrhea occurrence, OVA-specific antibody responses, and mast cell responses. These changes were accompanied by preservation of jejunal tight junction-related markers and modulation of T-cell-associated immune responses. In vitro, genistein modulated antigen uptake, maturation-associated features of bone marrow-derived dendritic cells (BMDCs), and BMDC-driven CD4⁺ T-cell polarization. In parallel, genistein-pretreated mice showed altered gut microbial structure, higher relative abundances of selected SCFA-associated taxa, increased fecal butyrate, and fecal metabolomic alterations involving purine metabolism, bile-acid-related metabolism, and tryptophan-related microbial metabolites. Consistently, correlation analyses indicated associations among microbial taxa, metabolites, immune indicators, and intestinal barrier markers. Together, these findings provide preliminary mechanistic insight into genistein in experimental FA and support further investigation of genistein as a dietary bioactive candidate for FA prevention. Full article

Porcine enteric coronaviruses (PECs), including porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV), remain major causes of neonatal diarrhea, dehydration, mortality, and economic loss in swine production. Despite substantial progress in vaccine development, durable field protection is still inconsistent. In this narrative review, this narrative review synthesizes current knowledge on PEC vaccine design from three connected perspectives: antigenic breadth, mucosal immunity, and translational evaluation. The economic and virological context of PEC vaccine development is first summarized, including the recurrent production burden of PECs, coronavirus genome organization, structural proteins, and the central role of the spike protein in receptor engagement, membrane fusion, and neutralizing antibody induction. Key issues are then discussed, including how spike diversity, conformational stability, epitope accessibility, glycan shielding, and antigen matching influence protective breadth; why intestinal secretory IgA, mucosal immune-cell trafficking, local memory responses, and lactogenic immunity should be prioritized as biologically relevant endpoints; and how delivery route, adjuvant selection, and platform design shape response quality. Current evidence on recombinant protein, viral-vectored, nanoparticle, virus-like particle, probiotic, plant-derived, and mRNA-based approaches is compared with attention to both promise and current evidentiary and translational limitations. The available literature suggests that future progress in PEC vaccinology is likely to depend less on platform novelty alone than on integrated vaccine designs that align antigen selection, mucosal delivery, maternal–neonatal protection, heterologous challenge, manufacturability, and field applicability. Full article

Snake venoms are rich sources of molecules with pharmacological potential, with approximately 90% of their composition consisting of proteins and peptides responsible for their biological activities. These proteins are classified as enzymatic or non-enzymatic. Enzymatic proteins function as catalysts in regulatory chemical reactions, whereas non-enzymatic proteins, despite lacking catalytic activity, play essential roles in physiological processes. Lectins are non-enzymatic proteins of non-immune origin characterized by carbohydrate- and glycoprotein-binding domains, enabling their ability to agglutinate erythrocytes. C-type lectins and C-type lectin-like proteins are commonly found in snake venoms and are associated with hemostatic disturbances, particularly bleeding and coagulation disorders. This review provides a comprehensive analysis of studies published over the past decade on lectins isolated from snake venom, addressing their definitions, classifications, structural characteristics, and mechanisms of action, as well as their relevance in biotechnological applications. Although progress has been made in elucidating their pharmacological properties, most studies have focused on plant lectins. In contrast, research on snake venom lectins remains limited, particularly regarding their heterologous activities. This gap, especially compared to other venom-derived molecules, highlights the need to further expand research on this class of proteins. Full article

Caspases orchestrate metazoan apoptosis, regulating processes such as embryogenesis, the death of old and infected cells and immune tolerance. Structural orthologs of caspases have been identified in bacteria, plants, protists and fungi and regulated cell death has been demonstrated in these organisms. This led some researchers to conclude that fungal metacaspases might perform a similar function to caspases. This review discusses regulated cell death, beginning with an account of RCD and the central role of caspases in mammalian RCD. It goes on to give examples of RCD in fungi, compares the structure and activity of caspase orthologs and outlines examples of metacaspase-dependent and metacaspase-independent cell death in fungi, focusing on S. cerevisiae. Finally, it addresses the question “are metacaspases caspases?”, identifies alternative cell death proteases and recommends future research objectives. Full article