Search Results (144)

Background/Objectives: The wall-associated kinases (WAKs) and WAK-like proteins (WAKLs) comprise a unique receptor-like kinase subfamily in plants, which have been shown to regulate plant development and defense responses by sensing cell wall-derived components, such as pectin or pectin fragments. In this study, we aimed to characterize the function of WAKL10 in flg22-triggered immunity in Arabidopsis. Methods: Through functional analyses of WAKL genes in Arabidopsis, we identified WAKL10 as the most pronouncedly induced WAKL member in response to flg22 treatment. Gain- and loss-of-function genetic analyses were performed to assess its role in flg22-triggered immune responses, including mitogen-activated protein kinase (MAPK) activation, reactive oxygen species (ROS) burst, and defense gene induction. Transgenic Arabidopsis plants expressing a kinase domain-deleted mutant (WAKL10-ΔK) were generated. Co-immunoprecipitation assays were conducted to examine interactions with FLAGELLIN-SENSITIVE 2 (FLS2) and BRI1-ASSOCIATED RECEPTOR KINASE 1 (BAK1). Heterologous overexpression of WAKL10 in tomato was also tested for bacterial disease resistance. Results: WAKL10 positively regulates flg22-triggered immune responses. Interestingly, WAKL10-ΔK retains the capacity to potentiate these responses. Co-immunoprecipitation assays showed that both wild-type WAKL10 and WAKL10-ΔK constitutively associate with FLS2 and BAK1. Overexpression of WAKL10 in tomato confers enhanced bacterial disease resistance. Conclusions: The extracellular domain of WAKL10 promotes FLS2-BAK1 complex formation, thereby contributing to flg22 signaling. This study reveals a new function of WAKLs, distinguished from their proposed role in sensing cell wall components. The functional conservation of WAKL10 suggests its potential application in engineering disease resistance in crop plants. Full article

In recent years, yeast glucan particles (YGPs) have garnered significant attention as novel oral drug delivery carriers, owing to their superior biocompatibility, specific targeting capabilities, and intrinsic immunomodulatory properties. The yeast cell wall is primarily composed of β-glucan and mannan, with minor amounts of proteins and lipids. Among these, β-1,3-glucan serves as the pivotal functional component. It not only provides a physical barrier protecting payloads from gastric acidity and enzymatic degradation but also functions as a targeting ligand. By specifically binding to M cells in Peyer’s patches and Dectin-1 receptors on macrophages and dendritic cells, β-1,3-glucan facilitates precise drug delivery to gut-associated lymphoid tissue (GALT) or macrophage-rich inflammatory sites. Consequently, β-1,3-glucan-based YGPs demonstrate immense potential in oral targeted delivery systems for macrophage-associated pathologies. However, native YGPs, constrained by their inherent porous architecture and relatively simple physicochemical properties, often fall short of meeting the complex requirements for precise encapsulation, controlled release, and multifunctionality. To address these limitations, current research is actively exploring the functionalization of YGPs with various composite materials to engineer advanced delivery platforms. This review introduces the composition, structural characteristics, and fabrication methodologies of YGPs, alongside their specific merits and limitations in oral drug delivery. Furthermore, it critically analyzes strategies for modifying YGPs with composite materials to overcome delivery barriers. Finally, the review discusses their therapeutic applications across various diseases and outlines future developmental trends. Full article

Particulate matter (PM) is a complex mixture of airborne solid particles and liquid droplets originating from various environmental sources, and it has been implicated in the initiation, development, and progression of pulmonary inflammation and respiratory diseases. However, the underlying associated molecular mechanisms remain unclear. Adenophora divaricate Franch. & Sav. (AD) is a medicinal herb classified within the Campanulaceae family and genus Adenophora, with a broad geographic distribution across East Asia, including Korea, Asia, and Russia. In this study, we investigated the mechanisms underlying the effects of AD on PM-induced lung inflammation in both PM-stimulated RAW264.7 cells and PM-exposed mice. Considering that the reactive oxygen species (ROS)-mediated thioredoxin-interacting protein (TXNIP) and NOD-like receptor pyrin domain containing (NLRP3) inflammasome pathway plays a role in PM-induced inflammatory responses, we focused on determining whether AD exerts its anti-inflammatory effects through modulation of this signaling pathway. The anti-inflammatory properties of the methanolic extract of AD were evaluated using PM-stimulated RAW264.7 cells and PM-exposed mice. PM was administered intranasally to mice for 7 days, whereas AD or dexamethasone was orally administered for the same duration. AD treatment significantly attenuated pulmonary inflammation, as evidenced by reduced inflammatory cell counts and decreased cytokine levels in bronchoalveolar lavage fluid. In addition, AD decreased oxidative stress marker (ROS and thiobarbituric acid reactive substances) while increasing glutathione content, leading to suppression of TXNIP/NLRP3 inflammasome expression. Histopathological analysis revealed a marked alleviation of inflammatory responses in lung tissue, characterized by diminished inflammatory cell infiltration and reduced alveolar wall thickening. Collectively, these findings suggest ROS-mediated TXNIP serves as a key regulatory factor, and AD may serve as a potential therapeutic agent for pulmonary inflammation. Full article

Bacterial wilt caused by Ralstonia solanacearum is a major constraint on tomato (Solanum lycopersicum L.) production, yet the molecular basis of quantitative resistance remains poorly understood. In this study, comparative transcriptome profiling was performed on resistant (‘ZM3’) and susceptible (‘ZM86’) tomato inbred lines following pathogen inoculation in roots, stems, and leaves. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify resistance-associated regulatory modules and hub genes. The results revealed distinct gene expression patterns between the two genotypes after infection. Several co-expression modules were significantly associated with resistance or susceptibility traits. Functional enrichment analysis showed that differentially expressed genes were mainly involved in plant hormone signal transduction, plant–pathogen interaction, phenylpropanoid biosynthesis, and cell wall modification. Genes related to ethylene and salicylic acid signaling were strongly induced following infection, whereas brassinosteroid-associated genes showed genotype-dependent expression patterns. Network analysis further identified several hub genes within defense-related modules, including ACO (Solyc04g007980), ERF1 (Solyc09g091950), MAPK9, receptor-like kinase RLK (Solyc07g006770), and a dirigent family gene (Solyc10g008900). Taken together, our results suggest that tomato resistance to Ralstonia solanacearum involves a coordinated defense network integrating hormone-mediated transcriptional regulation and structural reinforcement, and provides candidate genes for breeding bacterial wilt-resistant cultivars. Full article

Lysin motif (LysM) domain-containing proteins are widespread in prokaryotes and eukaryotes, and play crucial roles in microbe-host interactions. In recent decades, a large number of LysM domain-containing proteins have been identified and confirmed to participate in various biological processes, including microbial growth, fungal pathogenesis, and recognition of pathogens by plant immune receptors. Emerging evidence has shown that some LysM domain-containing proteins in plant pathogenic fungi have evolved as key virulence factors. They manipulate host immune responses mainly by interfering with the plant’s perception of chitin, a core pathogen-associated molecular pattern (PAMP) of fungal cell walls. However, the functions of LysM domain-containing proteins in plant pathogenic fungi have not been systematically summarized. In this review, we discuss the latest advances in the structural characteristics, classification, and functional mechanisms of these proteins, as well as their applications in plant disease control. We also propose the current challenges and future research directions in this field. This review aims to deepen the understanding of the molecular mechanisms underlying plant-fungal interactions mediated by LysM domain-containing proteins and provide theoretical references for developing novel and environmentally friendly strategies for fungal disease management in agriculture. Full article

Plants utilize cell surface pattern recognition receptors to recognize pathogen-associated molecular patterns (PAMPs) and activate pattern-triggered immunity (PTI) responses. Late blight, caused by the oomycete plant pathogen Phytophthora infestans, poses a major threat to global potato production. The oomycete PAMP, P. infestans cell wall ceramide D, triggers reactive oxygen species (ROS) production in potato and Arabidopsis. It is specifically recognized by the lectin receptor-like kinase RESISTANT TO DFPM-INHIBITION OF ABSCISIC ACID SIGNALING 2 (RDA2) in Arabidopsis. Treatment with P. infestans ceramide D enhances potato resistance against P. infestans. However, the function of RDA2 homologs in potato remains uncharacterized. Herein, potato RDA2 genes were identified through sequence alignment analysis. Their expression levels were subsequently measured in a potato inbred line infected with P. infestans. Notably, transient expression of StRDA2A, but not its kinase-dead mutant StRDA2A^K543M, caused cell death and enhanced disease resistance in Nicotiana benthamiana. Additionally, two RXLR-type effector proteins significantly inhibited StRDA2A-induced cell death. The findings of this study suggest that potato receptor kinase RDA2 proteins confer disease resistance, which is attenuated by RXLR effectors secreted by P. infestans. Full article

Plant defence elicitors have emerged as pivotal components of sustainable fruit crop protection, aligning with One Health principles by reducing chemical residues while enhancing ecosystem and human health. These exogenous agents—ranging from phytohormones, peptides, and cell-wall fragments to botanical extracts—activate or prime innate immune responses in fruit crops through pattern-triggered immunity (PTI), systemic acquired resistance (SAR), and induced systemic resistance (ISR) pathways. Over the last decade, advances in receptor biochemistry, genomics, metabolomics, and epigenetics have transformed this field. Recent mechanistic advances reveal that oligosaccharide elicitors derived from chitosan and laminarin are perceived by membrane-localised pattern recognition receptors (PRRs) that confer broad-spectrum resistance against fungal, bacterial, and viral pathogens in fruits. By contrast, no specific protein receptor has been identified for harpin proteins, the emerging evidence indicating that harpin perception may occur through direct interaction with plasma-membrane lipids or lipid-associated proteins. The One Health approach is supported by elicitors, biodegradability, minimal environmental persistence, and the ability to reduce synthetic fungicide usage by 30–70%. However, challenges remain regarding batch-to-batch variability, sensory acceptance due to bitter compounds, regulatory hurdles for novel food approvals, and the need for optimised application protocols that consider the fruit genotype and developmental stage. The future integration of nanotechnology for targeted delivery, the artificial-intelligence-driven screening of active molecules, and synergistic combinations with biocontrol agents promises to overcome these limitations, positioning plant defence elicitors as cornerstone tools for resilient, health-promoting fruit production systems. Full article

Introduction: The pro-inflammatory cytokine interleukin-17A (IL-17A) has a key role in the inflammatory cascade and promotes vascular inflammation and dysfunction. In addition, IL-17A is centrally involved in several autoimmune diseases. IL-17A deficiency has been linked to reduced vascular inflammation associated with attenuated arterial hypertension under long-term angiotensin II (Ang II) exposure for four weeks. This is of interest as IL-17A is one factor linking several autoimmune diseases with cardiovascular comorbidity. So far, little is known about the effects of IL-17A during the early stages of vascular dysfunction development—an interval possibly representing an optimal therapeutic window. Methods: Mice lacking the IL-17A receptor alpha (IL-17RAdel) and wild-type counterparts were treated with Ang II for one week (1 mg/kg bodyweight/week). We assessed systemic oxidative stress formation and vascular function, as well as inflammatory cells in the vessel wall. In parallel, C57BL/6J mice treated with Ang II received anti-IL-17A therapy, to evaluate the same parameters. Results: Both IL-17RA-deficient mice and anti-IL-17A-treated C57BL/6J mice exhibited an attenuated oxidative stress response and mitigated vascular inflammation following one week of Ang II treatment. These effects did not significantly prevent the onset of Ang II-induced vascular dysfunction at that timepoint. Conclusions: After one week of Ang II treatment, antagonizing IL-17RA or IL-17A only partially reduced/attenuated the Ang II-induced effects on the vasculature. In the context of IL-17A-driven autoimmune diseases with associated vascular pathology, our findings suggest that anti-inflammatory therapies alone may not be sufficient to attenuate vascular impairment. A combined approach including agents with direct protective vascular effects may be required for effective intervention for the associated vascular comorbidity. Full article

The pepper Bs2 resistance gene confers resistance to susceptible Solanaceae plants against pathogenic strains of Xanthomonas campestris pv. vesicatoria carrying the avrBs2 avirulence gene. Previously, we generated Bs2-transgenic Citrus sinensis plants that exhibited enhanced resistance to citrus canker caused by Xanthomonas citri subsp. citri (Xcc), although the underlying mechanisms remained unknown. To elucidate the molecular basis of the early defense response, we performed a comparative transcriptomic analysis of Bs2-expressing and non-transgenic plants 48 h after Xcc inoculation. A total of 2022 differentially expressed genes (DEGs) were identified, including 1356 up-regulated and 666 down-regulated genes. In Bs2-plants, 36.8% of the up-regulated DEGs were associated with defense responses and biotic stress. Functional annotation revealed major changes in genes encoding receptor-like kinases, transcription factors, hormone biosynthesis enzymes, pathogenesis-related proteins, secondary metabolism, and cell wall modification. Among hormone-related pathways, genes linked to ethylene biosynthesis and signaling were the most strongly regulated. Consistently, endogenous ethylene levels increased in Bs2-plants following Xcc infection, and treatment with an ethylene-releasing compound enhanced resistance in non-transgenic plants. Overall, our results indicate the Bs2 expression activates a complex defense network in citrus and may represent a valuable strategy for controlling canker and other Xanthomonas-induced diseases. Full article

Chronic kidney disease (CKD) accelerates vascular dysfunction and cardiovascular disease, partly through the accumulation of the uraemic toxin indoxyl sulphate (IS). Thrombospondin-1 (TSP1) and its receptor CD47 have been implicated in vascular pathology, but their role in CKD-associated vascular remodelling is unknown. We investigated the contribution of TSP1–CD47 signalling to vascular smooth muscle cell (VSMC) dysfunction in CKD. Human aortic VSMCs (hVSMCs) were exposed to IS, TSP1, or plasma from patients with CKD. CKD was induced in wild-type (WT) and CD47-deficient (CD47KO) mice using 5/6 nephrectomy. Vascular changes were assessed by histology, immunohistochemistry, and molecular analyses. IS, TSP1, and CKD plasma increased TSP1 expression in hVSMCs, reduced proliferation, elevated β-galactosidase activity, and activated phosphorylated ERK1/2 and cytoplasmic aryl hydrocarbon receptor. These effects were attenuated by CD47 blockade. CKD plasma further enhanced IS- and TSP1-induced senescence. In vivo, 5/6 nephrectomy induced aortic wall thickening in WT but not in CD47KO mice. Aortic pERK1/2 was reduced in CD47KO mice despite persistent TSP1 upregulation. IS and TSP1 promote VSMC senescence through CD47-dependent ERK1/2 and AhR signalling. CD47 deletion protects against CKD-induced vascular remodelling, suggesting that CD47 blockade may represent a novel therapeutic strategy to mitigate vascular complications in CKD. Full article

Given the limited efficacy of current interventions and the complexity of chronic pain, identifying perpetuating factors is crucial for uncovering new mechanistic pathways and treatment targets. The oral and gut microbiome has emerged as a potential modulator of pain through immune, metabolic, and neural mechanisms. Contemporary evidence indicates that chronic pain populations exhibit altered oral and gut microbiota, characterized by reduced short-chain fatty acid (SCFA)-producing taxa and an overrepresentation of pro-inflammatory species. These compositional changes affect metabolites such as SCFAs, bile acids, and microbial cell wall components, which interact with host receptors to promote peripheral and central sensitization. Microbiota-derived metabolites modulate peripheral sensitization by altering nociceptive neuron excitability and stimulating immune cells to release pro-inflammatory cytokines that increase blood–brain barrier permeability, activate microglia, and amplify neuroinflammation. Activated microglia further disrupt the balance between excitatory and inhibitory neurotransmission by enhancing glutamatergic activity and weakening GABAergic signaling, thereby contributing to the induction and maintenance of central sensitization. While observational studies establish associations between dysbiosis and chronic pain, animal models and early human fecal microbiota transplantation studies suggest a potential causal role of dysbiosis in pain, although human evidence remains preliminary and influenced by diet, lifestyle, and comorbidities. Overall, microbiota appears to regulate pain via peripheral and central mechanisms, and targeting it through specific interventions, such as dietary modulation to enhance SCFA production, alongside broader lifestyle measures like sleep, physical activity, stress management, and oral hygiene, may represent a new therapeutic strategy for the management of chronic pain. Full article

The plant plasma membrane serves as the primary interface for perceiving extracellular signals, a function largely mediated by plasma membrane receptors (PMRs). In wheat (Triticum aestivum), the functional characterization of these receptors is impeded by the species’ large, hexaploid genome, which results in extensive gene duplication and functional redundancy. This review synthesizes current knowledge on wheat PMRs, covering their diversity, classification, and signaling mechanisms, with a particular emphasis on their central role in plant immunity. We highlight the remarkable structural and functional diversification of PMR families, which range in size from 10 members, as seen in the case of wheat leaf rust kinase (WLRK), to over 3424 members in the receptor-like kinase (RLK) family. Furthermore, we reviewed the role of PMRs in being critical for detecting a wide array of biotic stimuli, including pathogen-associated molecular patterns (PAMPs), herbivore-associated molecular patterns (HAMPs), and symbiotic signals. Upon perception, PMRs initiate downstream signaling cascades that orchestrate defense responses, including transcriptional reprogramming, cell wall reinforcement, and metabolic changes. The review also examines the complex cross-talk between immune receptors and other signaling pathways, such as those mediated by brassinosteroid and jasmonic acid receptors, which underpin the delicate balance between growth and defense. Finally, we bridge these fundamental insights to applications in crop improvement, delineating strategies like marker-assisted selection, gene stacking, and receptor engineering to enhance disease resistance. After identifying key obstacles such as genetic redundancy and pleiotropic effects, we propose future research directions that leverage multi-omics, systems biology, and synthetic biology to fully unlock the potential of wheat PMRs for sustainable agriculture. Full article

Background: Although luteolin (Lut) is well recognized for its anti-inflammatory and antioxidant effects, its potential role in preventing vascular senescence remains underexplored in primary vascular aging. This study aimed to investigate the anti-vascular-aging effects of Lut in both cellular and murine aging models and to elucidate its conserved molecular mechanisms across species. Methods: Canine and feline vascular endothelial cells (cVECs and fVECs) were subjected to doxorubicin-induced senescence, while senescence-accelerated mice prone 8 (SAMP8) received an 8-week dietary supplementation with Lut. Senescence markers, inflammatory cytokines, antioxidant activities, vascular biomechanics, and histological changes were assessed. Transcriptomic and metabolomic analyses were combined to identify molecular pathways. Statistical significance was determined by one-way analysis of variance with Tukey’s or Games–Howell post hoc tests (p < 0.05). Results: Lut markedly reduced senescence-associated β-galactosidase activity, suppressed interleukin-6 and matrix metalloproteinase expression (p < 0.05), and enhanced superoxide dismutase activity and nicotinamide adenine dinucleotide levels (p < 0.05) in cVECs, fVECs, and SAMP8 sera. In aged mice, Lut alleviated arterial wall thickening and vascular inflammation, improved vascular biomechanics and systemic oxygenation (p < 0.05), and attenuated cardiac and hepatic inflammatory infiltration. Multi-omics analyses in cVECs revealed that Lut targets aldehyde dehydrogenase 1 to increase 9-cis retinoic acid, thereby activating the retinol X receptor–peroxisome proliferator-activated receptor (PPAR) network, which accelerates lipid clearance and oxidation. Consistent activation of this pathway was validated in murine vascular transcriptomes. Conclusions: These findings demonstrate that Lut delays vascular aging by activating the retinoic acid–PPAR axis and reprogramming lipid metabolism. This conserved mechanism was consistently observed in doxorubicin-induced cVEC senescence and the SAMP8 model, underscoring the robustness of Lut’s action across distinct contexts of vascular aging. Full article

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and poor clinical outcomes. Emerging evidence suggests that the tumor-associated microbiome may influence disease progression and therapy response. Methods: We investigated how the Gram-negative bacterium Pseudomonas aeruginosa and Gram-positive bacterium Staphylococcus aureus, together with their cell wall components lipopolysaccharide (LPS) and lipoteichoic acid (LTA), modulate doxorubicin (DOX) efficacy in TNBC cells. Using gentamicin protection combined with flow cytometry of eFluor 450-labeled bacteria and CFU quantification, we assessed bacterial uptake, persistence, and effects on drug response in MDA-MB-468, MDA-MB-231, and MDA-MB-453 cells. Results: Both bacteria entered TNBC cells and survived for several days in a cell line-dependent manner. Notably, bacterial infection and purified cell wall ligands (LPS and LTA) significantly increased DOX accumulation and enhanced cytotoxicity in MDA-MB-468 and MDA-MB-231, but not in MDA-MB-453. The similar effects of LPS and LTA implicate Toll-like receptor signaling (TLR2 and TLR4) in modulating drug uptake. Conclusions: These findings demonstrate that bacterial infection and associated ligands can enhance doxorubicin uptake and cytotoxicity in TNBC cells, implicating TLR signaling as a potential contributor. Our results highlight the importance of host–microbe interactions in shaping chemotherapy response and warrant further investigation into their therapeutic relevance. Full article

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins play evolutionarily conserved roles in intracellular vesicle trafficking and membrane fusion across eukaryotes. In pathogenic fungi, various SNARE homologs have been shown to critically regulate host infection processes. Here, we characterize the functional roles of CfSec22 in the sweet potato black rot pathogen Ceratocystis fimbriata. Phylogenetic and domain analyses demonstrate that CfSec22 shares homology with Sec22 proteins from Saccharomyces cerevisiae (ScSec22), Magnaporthe oryzae (MoSec22), and other fungi, containing both the characteristic Longin homology domain and V-SNARE domain. Functional studies reveal that CfSec22 regulates growth, conidiation, and virulence of C. fimbriata. Deletion of CfSEC22 resulted in abnormal vacuole morphology and impaired endocytosis. The ΔCfsec22 mutant displayed heightened sensitivity to diverse stress conditions: oxidative, endoplasmic reticulum, and cell wall stressors. Subcellular localization studies confirmed the endoplasmic reticulum residence of CfSec22. Finally, we established that CfSec22 regulates the secretion of virulence-associated proteins and is required for the induction of ipomeamarone in infected sweet potato tissues. Together, our findings demonstrate that CfSec22-mediated vesicle trafficking serves as a critical regulatory mechanism supporting growth, conidiogenesis, and pathogenicity in C. fimbriata. Full article