Search Results (2,850)

Plant metabolism is essential for coordinating growth, development, and defense under changing environmental conditions. Plants continuously adjust their metabolic pathways to balance resource allocation between growth and immune responses. Under stress, metabolic reprogramming redirects energy and resources toward the production of defense compounds and activation of immune signaling pathways. These changes involve complex interactions among primary metabolism, specialised metabolites, and regulatory networks, including calcium signaling, reactive oxygen species, and phytohormones. Advances in metabolomics and multi-omics technologies have improved understanding of the metabolic control of plant immunity; however, knowledge remains fragmented, and an integrated framework linking metabolism, development, and defense is still emerging. This review examines plant immunometabolism by highlighting the dynamic relationships between metabolic networks and immune functions during development and stress. It discusses pathways that influence growth, stress-induced metabolic shifts linked to defense, and how signaling interacts with metabolism. Progress in metabolomics, transcriptomics, proteomics, and computational modeling that supports systems-level analysis of plant metabolism is also summarized. In addition, potential applications in agriculture and biotechnology, including metabolic engineering, genome editing, and metabolomics-based breeding, are considered in relation to crop resilience. By integrating metabolism, signaling, and systems biology, this review provides a broad perspective on how metabolic reprogramming shapes the growth–defense trade-off in plants and outlines future directions for developing climate-resilient crops. Full article

The Mediterranean Diet (MD) is recognized for promoting longevity and reducing the risk of chronic disease, yet the mechanisms underlying these benefits remain uncharacterized. This review highlights the diverse nutritional and phytoactive constituents of the MD and research exploring its complex network of polyphenols. It discusses data evaluating MD-derived constituents formulated into a dietary supplement capsule developed using a systems and network biology framework. Component selection was based on their actions on enzyme systems involved in senescence-related pathways and health preservation. This review highlights how MD components synergistically modulate pathways central to antioxidant activity, cognitive health, and aging. Liquid chromatography–mass spectrometry identified phytochemically diverse constituents in capsules (supplied by DailyColors™, Warwickshire, UK and Sebastopol, CA, USA) derived from primary color groups in sixteen Mediterranean plants. These constituents were mapped to bioactive networks targeting enzymes linked to inflammation, metabolic regulation, and cellular senescence. Preclinical studies demonstrated the modulation of mitochondrial and metabolic health markers, with complementary effects on cytokine inhibition and glucose sensitivity. Two clinical studies confirmed broad proteomic and epigenetic effects on pathways governing immunity, skeletal muscle, cognition, and inflammation. Therefore, this review advances a novel perspective that MD polyphenols act through synergistic, multi-pathway interactions that link dietary patterns to coordinated regulation of longevity and healthy aging. Full article

Epigenetic regulation plays a central role in modulating plant immune responses and interactions with beneficial microbes. In this study, we investigated the contribution of RNA-directed DNA methylation (RdDM) components—DCL3; AGO9; DCL1; and the de novo DNA methyltransferases CMT3, DRM1, and DRM2—to the interaction between Arabidopsis thaliana, Trichoderma atroviride, and foliar pathogens. We show that DCL3 and AGO9 differentially regulate basal and inducible immunity, negatively affecting resistance to the necrotrophic fungus Botrytis cinerea, while promoting defense against the hemibiotrophic bacterium Pseudomonas syringae pv. tomato DC3000. Transcriptional analyses revealed that RdDM components modulate the balance between jasmonic acid/ethylene (JA/ET) and salicylic acid (SA) signaling pathways, influencing the amplitude and coordination of defense responses. In addition, DCL3 and DCL1 appear to be required for the full expression of T. atroviride-mediated systemic resistance, whereas AGO9 and DNA methyltransferases contribute to efficient root colonization. Notably, mutants in these pathways displayed enhanced basal resistance but impaired responsiveness to beneficial microbial signals, revealing a trade-off between constitutive defense activation and inducible systemic protection. Consistent with this, alterations in RdDM components were also associated with changes in plant growth dynamics under specific conditions, supporting a role for epigenetic regulation in coordinating growth–defense trade-offs. Together, our findings support a model in which epigenetic regulation controls defense responsiveness, enabling plants to balance immune activation, growth and compatibility toward beneficial microbes. Full article

Water-soluble carbohydrate (WSC) is the key to producing quality forage silage and an important energy source for ruminants. The aim of this study was to investigate the effect of different silages used as roughage sources [whole-plant sugarcane silage (WSS) vs. elephant grass silage (EGS)] with varying levels of WSC on silage quality, buffalo growth performance, apparent digestibility, rumen fermentation, and microbial communities. Sixteen healthy male crossbred buffaloes were randomly divided into two treatment groups, with eight buffaloes/treatment. One group was fed whole-plant sugarcane silage, and the other group was fed elephant grass silage. Compared with EGS, WSS had higher WSC, lactic acid, and ethanol, but lower pH, ammonia nitrogen, propionic acid, and butyric acid (BA) contents (p < 0.05). Potential probiotics (e.g., Lactiplantibacillus and Hanseniaspora) were more abundant in WSS than in EGS (p < 0.05). Moreover, the feed conversion rate was higher in HWS (p < 0.05). However, rumen fermentation parameters were unaffected by diet (p > 0.05). Moreover, feeding WSS had lower dry matter digestibility (DMD), organic matter digestibility (OMD), and lower acid detergent fiber digestibility (ADFD) (p < 0.05). After WSS feeding, ruminal Treponema_2 was strongly associated with DMD, OMD, and ADFD (p < 0.05), and also showed positive correlations with BA and PA contents in WSS (p < 0.05). Additionally, rumen Ruminiclostridium_5 and Pseudozyma was associated with DMD and ADFD after being fed EGS (p > 0.05), respectively, but the Pseudozyma was associated with BA (p < 0.05) and Clostridium_sensu_stricto_11 (p > 0.05) in EGS. Our findings indicated that WSS exhibited superior fermentation quality and harbored potential beneficial microbes, whereas EGS showed higher apparent nutrient digestibility in buffalo but also contained undesirable bacteria (e.g., Clostridium_sensu_stricto_11). Future research should investigate the long-term effects of WSS feeding on buffalo health, immunity, and production performance, as well as its impact on rumen microbiota stability, to fully assess its potential as a safe and sustainable roughage source. Full article

Transcription factor 19 (TCF19) is a multifunctional biomolecule located within the major histocompatibility complex (MHC) class I region on chromosome 6p21.3. Structurally, TCF19 contains a plant homeodomain (PHD) finger that recognizes histone H3 lysine 4 trimethylation (H3K4me3) and a forkhead-associated (FHA) domain with yet-uncharacterized functions. Emerging evidence positions TCF19 as a multifunctional regulator associated with cell cycle progression, transcriptional regulation, cancer progression, and immune modulation through epigenetic and signaling mechanisms. This review provides the first systematic synthesis of TCF19’s structural domains, regulatory networks, and context-dependent functions across cancer and non-cancer diseases. We highlight critical knowledge gaps, including the unresolved function of its FHA domain and the lack of direct small-molecule inhibitors. In cancer, TCF19 drives proliferation, metastasis, immune evasion, and therapy resistance. Beyond cancer, TCF19 is involved in metabolic diseases, chronic infections, inflammatory disorders, and sensory deficits. TCF19 serves as a promising molecular biomarker for cancer diagnosis, prognosis, and treatment response monitoring, though direct targeting strategies remain unavailable. Full article

Feed nutrition and rise in antibiotic resistance are growing global challenges in aquaculture, with Aeromonas hydrophila causing significant losses in the carp family. This 60-day study evaluated the potential of combining herbal seed extract (Achyranthes aspera and Ricinus communis) with inactivated vaccine (A. hydrophila) to enhance growth and immunity in Labeo rohita. A total of 540 fish were randomly assigned in six groups (T0-untreated control, T1-A. aspera seed extract (ASE), T2-R. communis seed extract (RSE), T3-vaccinated control, T4-vaccine plus ASE, T5-vaccine plus RSE). Results revealed that herbal–vaccine combinations, particularly T4, showed highest growth performance (p < 0.05). Furthermore, this group showed improved metabolic profiles, indicated by reduced serum cholesterol, triglycerides, and glucose, along with significantly elevated albumin and globulin concentrations. In terms of immune response, neutrophil counts were significantly higher in T4 and T5. Crucially, following a challenge with A. hydrophila, survival rates were higher in T4:90% and T5:85% compared with positive control’s meager 20% survival. Post-challenge hematology confirmed that groups T4 and T5 maintained an enhanced immune status. These findings suggest that combining medicinal plants extract with vaccine effectively enhances growth, immunity, and disease resistance in L. rohita, presenting an environment friendly alternative to traditional antibiotics in aquaculture. Full article

Colorectal cancer (CRC) remains one of the most prevalent malignancies worldwide and is the second largest contributor to both incidence and mortality, underscoring the urgent need for effective prevention strategies. This comprehensive review provides the most up-to-date evidence on the protective role of plant-based dietary patterns against CRC carcinogenesis, with particular emphasis on underlying cellular and molecular level mechanisms. Accumulating research demonstrates that plant-based foods, rich in dietary fibre, polyphenols, and multiple other bioactive compounds, promote gut microbial eubiosis, support immune regulation, and modulate adipose tissue homeostasis. These effects are accompanied by intestinal barrier integrity, enhanced production of short-chain fatty acids, and the induction of apoptosis in malignant cells. Moreover, plant-derived nutrients reduce the abundance of pro-inflammatory microbial taxa, decrease oxidative, nitrosative and carbonyl stress, and downregulate pro-inflammatory cytokines and signalling pathways, implicated in tumourigenesis. As a result, plant-based dietary patterns have high potential to reduce CRC risk through modulating the intricate interplay between epigenetics, inflammation, immune dysregulation, metabolic and hormonal disruptions, and gut microbiota, suggesting a highly promising, cost-effective and equitable strategy for CRC prevention. Full article

Both plants and animals have developed a sophisticated two-tiered innate immune system. This involves an initial recognition of microbial patterns conserved on the cell surface (PAMP-triggered immunity) and a subsequent more specific intracellular recognition of pathogenic effectors or their activities (effector-triggered immunity). A common fundamental feature is the use of NLR-like intracellular receptors to detect insider threats. Both plant NLRs (receptors containing nucleotide-binding domains and leucine-rich repeats) and animal NLRs (NOD-like receptors) share a modular tripartite architecture, typically featuring a central nucleotide-binding domain (NBD/NOD) and C-terminal leucine-rich repeats (LRRs). The NBD/NOD is crucial for facilitating the exchange of ADP/ATP, acting as a molecular switch to promote oligomerization and activation of NLRs in both kingdoms. In this review, we summarize the similarities and differences between plant and animal molecular perception and immunity mechanisms. Additionally, we highlight the fact that some human pathogens can infect plants, and crucially, some plant pathogens are capable of causing disease in humans. This suggests conserved molecular strategies to invade and manipulate host cells belonging to different biological kingdoms, uncovering that plant and human pathology may benefit from future investigations in their respective fields. Full article

Cow’s milk allergy (CMA) remains one of the most common food allergies in infancy, requiring the avoidance of cow’s milk and its derivatives. Breast milk is the best source of nutrition for infants. For those infants with CMA whose mothers are unable to breastfeed or choose not to, extensively hydrolysed formulas (eHFs) are widely recommended as first-line milk substitutes, whereas hydrolysed rice formulas (HRFs) are increasingly recognised as a viable alternative. This concept paper provides a healthcare professional (HCP) perspective on HRF, drawing on expert consensus from two meetings convened in 2025. Discussions noted the long history of safe and effective HRF use in Europe, its nutritional adequacy, and the evolving international guidelines supporting HRF as an alternative first-line option. A key meeting outcome was the development of a practical decision tree to help UK clinicians decide when HRF should be the preferred choice. Key considerations for its use in non-breastfed infants include the following: parental/caregiver stress related to persistent symptoms; ongoing symptoms despite multiple interventions; cultural and lifestyle choices; religious dietary requirements; and specialists’ recommendations. Secondary considerations highlighted by HCPs include the following: proven reactions whilst infants are breast-milk-fed together with parental request for formula; faltering growth; multiple symptoms; taste acceptance (older infants); and parental preference based on experience. The role of functional components, such as prebiotics and human milk oligosaccharides (HMOs), was noted in regard to the emerging evidence of benefits to the microbiome and immune development. The experts emphasised the importance of engaging HCPs across all levels of CMA care and addressing challenges in translating current guidance into treatment practice. It was concluded that, overall, HRF represents a nutritionally complete, plant-based alternative that has been shown to be well tolerated (taste, symptoms) in clinical studies. It can be used to broaden therapeutic options for infants with CMA in the UK who are not exclusively fed breast milk. Full article

Alternaria brown spot, caused by the tangerine pathotype of Alternaria alternata, is a destructive fungal disease affecting citrus production worldwide. Nucleotide-binding site-leucine-rich repeat (NBS-LRR) genes constitute a major class of plant immune receptors; however, their genome-wide characteristics and potential association with Alternaria brown spot resistance loci in citrus remain poorly understood. In this study, we performed a comprehensive genome-wide identification and comparative analysis of NBS-LRR genes across representative citrus species. A total of 417 and 326 NBS-LRR genes were identified in Citrus reticulata and Citrus clementina, respectively, and were classified into NL, CNL, TNL, and RNL subfamilies based on domain architecture. Phylogenetic reconstruction, gene structure analysis, conserved motif composition, chromosomal distribution, synteny relationships, and promoter cis-element profiling collectively revealed considerable structural variation and lineage-specific expansion of the NBS-LRR gene family in citrus genomes. By integrating previously reported quantitative trait locus (QTL) data for Alternaria brown spot, we identified several NBS-LRR genes located within a resistance-associated genomic interval on chromosome 3. Among these, a candidate gene, designated LRR2, exhibited differential transcriptional responses upon pathogen inoculation and displayed distinct sequence variations between citrus genotypes. Structural modeling and molecular docking analyses suggested potential binding interfaces between LRR2 and multiple host-selective toxins, although the biological relevance of these interactions requires further experimental validation. Subcellular localization assays in Nicotiana benthamiana showed that LRR2 is distributed in both the nucleus and cytoplasm. Notably, transient overexpression of LRR2 triggered hypersensitive response-like cell death and H₂O₂ accumulation. Collectively, this study provides a comprehensive overview of the citrus NBS-LRR gene family and presents a multifaceted characterization of a QTL-anchored candidate gene. These findings establish a genomic and molecular framework for further functional investigations of citrus–Alternaria interactions. Full article

Two-pore channels (TPCs) are evolutionarily conserved intracellular cation channels found in both plants and animals, where they mediate ion fluxes across endomembrane compartments. While historically the plant channel was among the first plant ion channels to be characterized, thanks to the relative ease of applying the patch-clamp technique to isolated plant vacuoles, where it is localized, the functional properties of the two main human isoforms, HsTPC1 and HsTPC2, expressed in endosomal and lysosomal membranes, were elucidated much later. In plants, TPCs are typically represented by a single isoform, exemplified by AtTPC1 in the model plant Arabidopsis thaliana, which functions as a voltage-dependent, Ca²⁺-regulated channel. The physiological role of plant TPCs is not yet fully clarified, although evidence suggests that they may contribute to systemic signaling and stress responses. In humans, two main isoforms, HsTPC1 and HsTPC2, are expressed in endosomal and lysosomal membranes. Human TPCs are primarily regulated by the phosphoinositide PI(3,5)P₂ and display a high selectivity for Na⁺. However, these channels also appear as a non-selective cationic conductance when activated by the potent Ca²⁺-mobilizing messenger NAADP, likely through interaction with an accessory protein. Functionally, human TPCs are involved in endolysosomal trafficking, membrane fusion, and intracellular signaling, with emerging roles in immunity, metabolism, and disease. Overall, TPCs represent key components of intracellular ion homeostasis and cellular physiology; however, their precise regulatory mechanisms and integrated physiological roles remain only partially understood and, in several respects, are still elusive. Full article

Salicylic acid (SA) is a key endogenous regulator involved in plant defense responses to biotic and abiotic stresses. The increasing resistance of pathogens to chemical plant protection products and growing environmental restrictions have intensified the search for alternative strategies to enhance plant health and stress tolerance. Among these strategies, the induction of natural defense mechanisms, in which SA plays a central signaling role, has gained particular attention. This review summarizes current knowledge on the role of SA in shaping plant resistance to environmental factors. The fundamental mechanisms of plant defense, including innate immunity, induced systemic resistance (ISR), and systemic acquired resistance (SAR), are discussed, with emphasis on the signaling function of SA and its interaction with other phytohormones, especially jasmonic acid and ethylene. The role of SA in regulating physiological processes associated with stress tolerance, such as antioxidant system activity, photosynthesis, plant growth, and senescence, is highlighted. The review of research results indicates that appropriately selected doses and timing of SA treatments can enhance resistance to selected pathogens and improve plant tolerance to adverse environmental conditions. However, treatment effectiveness depends on multiple factors, particularly SA concentration and plant–pathogen interactions. Salicylic acid is a promising component of integrated and sustainable plant protection strategies. Further research, especially under field conditions, is necessary to optimize its practical use and fully determine its potential in modern agriculture. Full article

Cardiovascular disease (CVD) is the world’s leading cause of death and continues to rise in prevalence, contributing to healthcare and economic costs. Following diagnosis, patients are advised to adopt medication regimens, increase physical activity, and modify dietary intake to reduce disease progression and prevent additional comorbidities. Oxalate is a small molecule in plant-derived foods such as spinach, potatoes, almonds, and peanuts and is also produced endogenously. Although oxalate is traditionally studied in the context of kidney stone disease, recent evidence suggests that it may be a dietary contributor to inflammation and oxidative stress in CVD. Elevated systemic oxalate levels promote reactive oxygen species (ROS) generation and activate inflammatory pathways such as nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and the NLRP3 inflammasome, which are key players in CVD. In this narrative review, we discuss the current literature describing the role of inflammation in CVD and evaluate emerging evidence that dietary oxalate may influence immune, oxidative, and vascular mechanisms contributing to CVD development and progression. In addition, we highlight populations that may be most vulnerable to oxalate-mediated vascular effects. We conclude by describing existing gaps in knowledge and potential future directions for the field. Understanding these mechanisms further may guide dietary recommendations and delineate oxalate’s potential role as a modifiable risk factor for CVD. Full article

Tissue repair is a finely organized process that progresses via a series of phases, including hemostasis, inflammation, proliferation, and remodeling, which are coordinated by immune–stromal interactions. Aging profoundly dysregulates these processes through mechanisms such as immunosenescence and inflammaging, cellular senescence, chronic inflammation, and extracellular matrix alterations, ultimately contributing to typical age-related progression. This review discusses the immune mechanisms that govern physiological tissue healing, as well as the age-related perturbations that lead to ulcerative and fibrotic diseases. It also highlights the potential application of extracellular vesicles (EVs), both mammalian and plant-derived, as a stable and low-immunogenicity mediator to modulate and re-establish repair homeostasis. Translational hurdles such as EV standardization, dosing, safety assessment, and manufacturing are critically discussed to promote their use in geroscience, regenerative medicine, and dermatology. Full article

Nutrient-sensing nuclear receptors (NSNRs), including PPARs, FXR, LXRs, RAR/RXR, VDR, and related orphan receptors, integrate a molecular interface that allows diet to communicate directly with the genome. By binding fatty acids, bile acids, sterols, vitamins, polyphenols, and other food-derived metabolites, NSNRs translate qualitative and quantitative features of the diet into coordinated transcriptional programmes across metabolically active organs. This ligand-dependent signalling network integrates dietary information to orchestrate inter-organ lipid and glucose metabolism, mitochondrial function, thermogenesis, and immune response, thereby enabling the organism to adapt dynamically to fasting–feeding cycles. In this review, we synthesise current evidence on the integrated roles of major NSNRs in the liver, skeletal muscle, white and brown adipose tissue, and kidney, emphasising how receptor networks within and between metabolic organs collectively govern energy expenditure, substrate partitioning, and systemic metabolic flexibility. We propose a conceptual framework in which diet functions as an “external endocrine organ”, acting as the primary source of chemically diverse NSNR ligands, while metabolic tissues serve as secondary signal amplifiers and integrators. Through circulating lipid species, bile acids, oxysterols, and other metabolites, these organs engage in continuous bidirectional communication that reprograms NSNR activity across tissues. We then examine how the global shift from minimally processed, nutrient-rich foods to nutrient-poor, energy-dense ultra-processed diets leads to a reduction in NSNR ligand diversity, promoting hepatic steatosis, muscle metabolic inflexibility, adipose tissue dysfunction, renal lipotoxicity, and chronic low-grade inflammation, ultimately causing obesity, type 2 diabetes, and cardiometabolic disease. Finally, we explore strategies to restore NSNR function, including Mediterranean and plant-based dietary patterns, as well as diets enriched with ω-3 polyunsaturated fatty acids, monounsaturated fats, and polyphenols. By integrating molecular, physiological, and clinical evidence, this review aims to clarify how NSNR networks translate dietary cues into coordinated inter-organ metabolism and how nutrient-poor diets lead to metabolic diseases trough a loss of metabolic information, rather than merely by energy excess. This framework supports a paradigm shift from calorie-centred nutrition to diet quality as the main therapeutic target for preventing metabolic diseases and promoting health. Full article