Search Results (80)

Silver nanoparticles (AgNPs), lauded for their unique antibacterial and physicochemical attributes, are proliferating across industrial sectors, raising concerns about their environmental fate, in aquatic systems. While “green” synthesis offers a sustainable production route with reduced chemical byproducts, the safety of these AgNPs for aquatic fauna remains uncertain due to nanoparticle-specific effects. Conversely, mast cells play crucial roles in fish immunity, orchestrating innate and adaptive immune responses by releasing diverse mediators and recognizing danger signals. Goblet cells are vital for mucosal immunity and engaging in immune surveillance, regulation, and microbiota interactions. The interplay between these two cell types is critical for maintaining mucosal homeostasis, is central to defending against fish diseases and is highly responsive to environmental cues. This study investigates the acute dermatotoxicity of environmentally relevant AgNP concentrations (0, 0.031, 0.250, and 5.000 μg/L) on zebrafish epidermis. A 96 h assay revealed a biphasic response: initial mucin hypersecretion at lower AgNP levels, suggesting an early stress response, followed by a concentration-dependent collapse of mucosal integrity at higher exposures, with mucus degradation and alarm cell depletion. A rapid and generalized increase in epidermal mucus production was observed across all AgNP exposure groups within two hours of exposure. Further mechanistic insights into AgNP-induced toxicity were revealed by concentration-dependent alterations in goblet cell dynamics. Lower AgNP concentrations initially led to an increase in both goblet cell number and size. However, at the highest concentration, this trend reversed, with a significant decrease in goblet cell numbers and size evident between 48 and 96 h post-exposure. The simultaneous presence of neutral and acidic mucins indicates a dynamic epidermal response suggesting a primary physical barrier function, with acidic mucins specifically upregulated early on to enhance mucus viscosity, trap AgNPs, and inhibit pathogen invasion, a clear defense mechanism. The subsequent reduction in mucin-producing cells at higher concentrations signifies a critical breakdown of this protective strategy, leaving the epidermis highly vulnerable to damage and secondary infections. These findings highlight the vulnerability of fish epidermal defenses to AgNP contamination, which can potentially compromise osmoregulation and increase susceptibility to threats. Further mechanistic research is crucial to understand AgNP-induced epithelial damage to guide sustainable nanotechnology. Full article

Systemic mastocytosis (SM) is a rare and heterogeneous disorder characterized by clonal proliferation and accumulation of neoplastic mast cells in one or more organs, most commonly the bone marrow, liver, spleen, and skin. Among its clinical variants, aggressive SM (ASM) presents organ damage and debilitating symptoms due to extensive mast cell infiltration. The management of ASM remains challenging, primarily because treatment must address both symptom control and disease progression. Background/Objectives: Recent therapeutic approaches have focused on tyrosine kinase inhibitors (TKIs) that target the oncogenic KIT driver mutation, predominantly the D816V mutation, which is implicated in mast cell proliferation. We report a case series of four patients diagnosed with ASM to highlight the real-world experience in the management of ASM. All patients had confirmed KIT D816V mutations and presented with signs of advanced organ dysfunction, such as marked hepatosplenomegaly, cytopenia, and significant bone marrow infiltration. First-line therapies, including cytoreductive agents or other TKIs were used. Responses varied in these patients, and ultimately, they were initiated on or transitioned to midostaurin, a multikinase TKI. Results: All four patients, after the initiation of midostaurin, presented clinical and biological improvement—at least a clinical improvement response according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment & European Competence Network on Mastocytosis (IWG-MRT-ECNM) criteria. These findings highlight the benefits of KIT inhibition in managing ASM, especially for patients with inadequate responses to traditional therapies. The impact of midostaurin on organ function, mast cell burden, and symptom control emphasizes the importance of the timely integration of TKIs into therapeutic protocols. However, optimal treatment duration, long-term safety, and the development of acquired resistance remain critical questions that warrant further studies. Larger prospective trials are needed to better delineate the prognostic factors associated with sustained response, refine patient selection, and explore combination strategies that may enhance therapeutic efficacy. Conclusions: The patients presented in this case series benefited from midostaurin therapy, showing either a clinical improvement or partial response according to the IWG-MRT-ECNM criteria. Our case series illustrates that KIT inhibitors can offer meaningful clinical benefit in ASM, reinforcing their position as an emerging cornerstone option in ASM management. Full article

Chronic, non-resolving inflammation is a major contributor to impaired wound healing in diabetes. Annexin A1 (AnxA1), a pro-resolving mediator, and its mimetic peptide Ac_2–26 have demonstrated therapeutic potential in modulating inflammatory responses. In this study, we evaluated the effects of topical Ac_2–26 hydrogel in a streptozotocin-induced diabetic wound model. Treatment significantly accelerated wound closure, improved tissue architecture, and reduced leukocyte infiltration. Immunohistochemical analysis revealed diminished mast cell accumulation and IL-1β expression in treated wounds. Complementary transcriptomic profiling supported the downregulation of pro-inflammatory genes, including Il1b and mast cell-related mediators, confirming the peptide’s regulatory effect on the wound immune landscape. Mounting evidence suggests that dysregulated mast cell activity plays a role in the heightened inflammatory tone and delayed tissue repair observed in diabetic wounds. In our model, Ac_2–26 hydrogel treatment attenuated IL-1β expression, suggesting an indirect downregulation of NLRP3 inflammasome activation, potentially mediated through mast cell modulation, though effects on other cell types within the wound microenvironment cannot be excluded. While definitive causality cannot be assigned, the integration of histological and transcriptomic data highlights mast cells as contributors to the IL-1β-driven inflammatory burden in diabetic wounds. These findings underscore the immunomodulatory capacity of Ac_2–26 and its potential to restore resolution pathways in chronic wound settings, positioning it as a promising candidate for future therapeutic development. Full article

Background: The escalating prevalence of food allergies, alongside the global call for environmentally sustainable dietary transitions, has drawn attention to plant-based dietary models—particularly those inspired by the EAT-Lancet Commission. These frameworks not only reduce reliance on animal-sourced foods, benefiting planetary health, but may also play a role in modulating immune tolerance and allergic responses. Methods: This scoping review followed PRISMA guidelines and included 53 peer-reviewed studies published between 2000 and 2024, retrieved from PubMed, Scopus, and Google Scholar. Eligible articles were classified into two thematic domains: prevention of food allergy onset (n = 31) and modulation of allergic symptoms in sensitized individuals (n = 22). Included studies comprised randomized controlled trials (n = 6), observational studies (n = 17), systematic reviews and meta-analyses (n = 11), and narrative/scoping reviews (n = 19). Results: Sustainable plant-based diets were consistently associated with a lower incidence of allergic sensitization and reduced symptom severity. These effects were partly due to the exclusion of common allergens (e.g., dairy, eggs, and shellfish) but more importantly due to immunomodulatory mechanisms. Fermentable fibers can enhance short-chain fatty acid (SCFA)-producing bacteria (e.g., Faecalibacterium prausnitzii), elevating butyrate and acetate levels, which interact with G-protein-coupled receptors 43 and 109A (GPR43 and GPR109A) to induce regulatory T cells (Tregs) and reinforce epithelial integrity via tight junction proteins such as occludin and claudin-1. Polyphenols (e.g., quercetin and luteolin) can inhibit Th2-driven inflammation by stabilizing mast cells and downregulating IL-4 and IL-1. Conclusions: Following sustainable dietary guidelines such as those proposed by the EAT-Lancet Commission may confer dual benefits: promoting environmental health and reducing the burden of allergic diseases. By emphasizing plant-based patterns rich in fiber and polyphenols, these diets support microbiota-mediated immune education, mucosal barrier function, and immunological tolerance. When properly supervised, they represent a promising tool for allergy prevention and symptom management. Larger randomized trials and long-term population studies are needed to confirm and operationalize these findings in clinical and public health contexts. Full article

Chitosan–hydroxyapatite (CS-HAp) biocomposites, combining the biocompatibility and bioactivity of chitosan with the osteoconductive properties of hydroxyapatite, are emerging as promising candidates for tissue engineering applications. These materials consistently exhibit excellent cytocompatibility, with cell viability rates greater than 95% in MTT and Neutral Red Uptake assays, and minimal cytotoxicity, as demonstrated by low levels of cell death in DAPI and Trypan blue staining. More importantly, CS-HAp biocomposites modulate the immune environment by enhancing the expression of anti-inflammatory cytokines (IL-10 and IL-4) and the pro-inflammatory cytokine TGF-β, while avoiding significant increases in TNF-α, IL-6, or NF-κB expression in fibroblast cells exposed to HAC and HACF scaffolds. In an in vivo dermatitis model, these biocomposites reduced mast cell counts and plasma histamine levels and significantly decreased pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), JAK1/3, VEGF, and AnxA1 levels. Structurally, HACF scaffolds demonstrated larger average pore sizes (95 µm) compared to HAC scaffolds (74 µm), with porosities of 77.37 ± 2.4% and 65.26 ± 3.1%, respectively. These materials exhibited high swelling ability, equilibrium water content, and controlled degradation over a week in culture media. In addition to their immunomodulatory effects, CS-HAp composites promote essential cellular activities, such as attachment, proliferation, and differentiation, thereby supporting tissue integration and healing. Despite these promising findings, significant gaps remain in understanding the underlying mechanisms of immune modulation by CS-HAp biocomposites, and formulation-dependent variability raises concerns about reproducibility and clinical application. Therefore, a comprehensive review is essential to consolidate existing data, identify key knowledge gaps, and standardize the design of CS/HAp composites for broader clinical use, particularly in immunomodulatory and regenerative medicine contexts. Full article

Asthma is a chronic and multifaceted respiratory condition that affects over 300 million individuals across the globe. It is characterized by persistent inflammation of the airways, which leads to episodes of wheezing, breathlessness, chest tightness, and coughing. The most prevalent form of asthma is classified as Type 2 or T2-high asthma. In this variant, the immune response is heavily driven by eosinophils, mast cells, and T-helper 2 (Th2) cells. These components release a cascade of cytokines, including interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13). This release promotes several processes: the production of immunoglobulin E (IgE), which is integral to allergic responses; the recruitment of eosinophils—white blood cells that contribute to inflammation and tissue damage. Conversely, non-Type 2 or T2-low asthma is typically associated with a different inflammatory profile characterized by neutrophilic inflammation. This type of asthma is driven by T-helper 1 (Th1) and T-helper 17 (Th17) immune responses, which are often present in older adults, smokers, and those suffering from more severe manifestations of the disease. Among asthmatic patients, approximately 80–85% of cases are classified as T2-high asthma, while only 15–20% are T2-low asthma. Treatment of asthma focuses heavily on controlling inflammation. Inhaled corticosteroids remain the cornerstone therapy for managing T2-high asthma. For more severe or treatment-resistant cases, biologic therapies targeting specific inflammatory pathways, such as anti-IgE (omalizumab), anti-IL-5 (mepolizumab, benralizumab), and anti-IL-4/IL-13 (dupilumab), have shown great promise. For T2-low asthma, macrolide antibiotics like azithromycin and other novel therapies are being explored. This article reviews the safety, efficacy, and indications of the currently approved biologics and discusses potential novel biologics for asthma. Full article

Background and Aims: In this research, we sought to enhance our comprehension of liver cancer’s genetic architecture by employing Mendelian randomization (MR) techniques to establish causative relationships between particular genetic variations and liver cancer susceptibility. Methods: We integrated data from the public databases with MR analysis to identify differentially expressed genes (DEGs) associated with Hepatocellular Carcinoma (HCC). We conducted functional enrichment analyses to determine the biological processes and signaling cascades associated with the identified DEGs. We also used the CIBERSORT deconvolution method to evaluate immune cell composition in HCC tissues, followed by correlation studies examining relationships between our key genes of interest and various immune cell populations. Additionally, we validated our findings using a rat model of HCC and clinical HCC samples. Results: We obtained two key genes, EHD4 and PPARGC1A, which co-regulated M0 macrophages, suggesting their role in macrophage polarization and tumor progression. In addition, PPARGC1A is associated with resting and activated mast cells, suggesting its involvement in regulating the tumor microenvironment. Detection of rat and clinical samples further confirmed the upregulation of these genes in HCC, supporting their potential as therapeutic targets. Conclusions: Our findings emphasize the significant involvement of EHD4 and PPARGC1A in HCC, specifically regarding their influence on tumor-associated macrophage polarization and broader immune microenvironment modulation. These findings offer new insights into the molecular mechanisms driving HCC and suggest that targeting these genes may provide novel strategies for personalized treatment. Full article

Palmitoylethanolamide (PEA) is an endogenous lipid mediator belonging to the N-acyl-ethanolamine family, widely recognized for its multifaceted effects on neuroprotection, chronic pain management, and immune modulation. As a naturally occurring compound, PEA plays a crucial role in maintaining homeostasis under conditions of cellular stress and inflammation. Its pharmacological effects are primarily mediated through peroxisome proliferator-activated receptor-alpha (PPAR-α) activation, alongside indirect modulation of cannabinoid receptors CB1 and CB2, as well as interactions with novel targets such as GPR55 and TRPV1. These molecular mechanisms underpin its broad therapeutic potential, particularly in the management of neuroinflammatory and neurodegenerative disorders, pain syndromes, and immune dysregulation. A major advancement in PEA research has been the development of ultramicronized palmitoylethanolamide (umPEA), which significantly enhances its bioavailability and therapeutic efficacy by facilitating better tissue absorption and interaction with key molecular pathways. Preclinical and clinical studies have demonstrated that umPEA is particularly effective in reducing neuroinflammation, stabilizing mast cells, and enhancing endocannabinoid system activity, making it a promising candidate for integrative approaches in neuropsychiatric and chronic inflammatory diseases. Given its well-established safety profile, umPEA represents an attractive alternative or adjunct to conventional anti-inflammatory and analgesic therapies. This communication provides a comprehensive overview of the mechanisms of action and therapeutic applications of both PEA and umPEA, emphasizing their emerging role in clinical practice and personalized medicine. Full article

Background: Irritable bowel syndrome (IBS) significantly impairs the lifestyle and quality of life of the global population. However, the underlying pathophysiological mechanisms remain largely elusive. While conventional pharmacological approaches show limited therapeutic efficacy, emerging microbiota-targeted dietary interventions present promising alternatives. Objectives: The present study aimed to elucidate the molecular mechanisms by which a synbiotic mitigates IBS and associated colonic dysfunctions in C57BL/6 mice. Methods: The mouse model was induced by a Citrobacter rodentium (C. rodentium) infection combined with water avoidance stress (WAS). Galacto-oligosaccharides (GOS) were identified as the optimal carbon source for the growth of Lactobacillus plantarum ZYC501 (L. plantarum ZYC501), leading to the establishment of the synbiotic formulation. Results: The 32-day synbiotic intervention, consisting of L. plantarum ZYC501 (1 × 10⁹ CFU/day) and GOS (10 g/L, w/w), significantly alleviated colonic transit dysfunction, visceral hypersensitivity, and anxiety-like behaviors in IBS mice. The synbiotic treatment significantly inhibited the expression levels of histamine, mast cell tryptase, and prostaglandin E2 (PGE2) (p < 0.05). The synbiotic also suppressed colonic inflammation by reducing the levels of lipopolysaccharide (LPS), TNF-α, and IL-6 (p < 0.05). Moreover, the synbiotic increased the expression of MUC2 and the production of short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate (p < 0.05). In terms of gut microbiota modulation, the synbiotic reshaped the gut microbiota composition, increasing the abundance of Lactobacillus and Akkermansia while decreasing the levels of Helicobacter and Saccharibacteria. Correlation analysis further revealed a strong association among SCFAs, colonic inflammation, and the gut microbiota. Conclusions: In conclusion, the synbiotic composed of L. plantarum ZYC501 and GOS effectively alleviates IBS and associated colonic dysfunctions by modulating the gut microbiota, reducing mast cell hyperactivity, and enhancing colonic barrier integrity. These findings provide a theoretical basis for developing gut microbiota-targeted dietary interventions for the management of IBS and improvement in gut health. Full article

Hypertension-induced cardiac remodeling is a complex process driven by interconnected molecular and cellular mechanisms that culminate in hypertensive myocardium, characterized by ventricular hypertrophy, fibrosis, impaired angiogenesis, and myocardial dysfunction. This review discusses the histomorphometric changes in capillary density, fibrosis, and mast cells in the hypertensive myocardium and delves into the roles of key regulatory systems, including the apelinergic system, vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathways, and nitric oxide (NO)/nitric oxide synthase (NOS) signaling in the pathogenesis of hypertensive heart disease (HHD). Capillary rarefaction, a hallmark of HHD, contributes to myocardial ischemia and fibrosis, underscoring the importance of maintaining vascular integrity. Targeting capillary density (CD) through antihypertensive therapy or angiogenic interventions could significantly improve cardiac outcomes. Myocardial fibrosis, mediated by excessive collagen deposition and influenced by fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta (TGF-β), plays a pivotal role in the structural remodeling of hypertensive myocardium. While renin–angiotensin–aldosterone system (RAAS) inhibitors show anti-fibrotic effects, more targeted therapies are needed to address fibrosis directly. Mast cells, though less studied in humans, emerge as critical regulators of cardiac remodeling through their release of pro-fibrotic mediators such as histamine, tryptase, and FGF-2. The apelinergic system emerges as a promising therapeutic target due to its vasodilatory, anti-fibrotic, and cardioprotective properties. The system counteracts the deleterious effects of the RAAS and has demonstrated efficacy in preclinical models of hypertension-induced cardiac damage. Despite its potential, human studies on apelin analogs remain limited, warranting further exploration to evaluate their clinical utility. VEGF signaling plays a dual role, facilitating angiogenesis and compensatory remodeling during the early stages of arterial hypertension (AH) but contributing to maladaptive changes when dysregulated. Modulating VEGF signaling through exercise or pharmacological interventions has shown promise in improving CD and mitigating hypertensive cardiac damage. However, VEGF inhibitors, commonly used in oncology, can exacerbate AH and endothelial dysfunction, highlighting the need for therapeutic caution. The NO/NOS pathway is essential for vascular homeostasis and the prevention of oxidative stress. Dysregulation of this pathway, particularly endothelial NOS (eNOS) uncoupling and inducible NOS (iNOS) overexpression, leads to endothelial dysfunction and nitrosative stress in hypertensive myocardium. Strategies to restore NO bioavailability, such as tetrahydrobiopterin (BH₄) supplementation and antioxidants, hold potential for therapeutic application but require further validation. Future studies should adopt a multidisciplinary approach to integrate molecular insights with clinical applications, paving the way for more personalized and effective treatments for HHD. Addressing these challenges will not only enhance the understanding of hypertensive myocardium but also improve patient outcomes and quality of life. Full article

Particulate matter (PM) exposure is known to induce significant ocular surface inflammation, necessitating effective therapeutic interventions. This study compared the efficacy of 2% rebamipide (REB) with 0.1% hyaluronic acid (HA) eye drops in investigating the anti-inflammatory and pathogen-clearance effects in a PM-induced ocular surface inflammation model using Sprague–Dawley (SD) rats. Parameters including clinical signs, histological changes, mucin secretions, inflammatory cytokines, mast cell degranulation, dysregulated cell proliferation, and cellular apoptosis were evaluated. 2% REB alleviated ocular surface inflammation by downregulating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inflammatory pathway and upregulating epidermal growth factor receptor (EGFR) signaling, thereby enhancing mucin secretion and promoting pathogen clearance. Histopathological analysis, western blot, and immunohistochemical staining revealed a marked reduction in inflammatory markers including MMP-9, IL-1β, TNF-α, IL-17, and CD-4, decreased mast cell degranulation, increased goblet cell density, and enhanced expression of mucins, including MUC5AC and MUC16, in the 2% REB-treated group compared to the 0.1% HA-treated and PM-exposed groups. Moreover, 2% REB demonstrated decreased apoptosis (TUNEL) and reduced uncontrolled cell proliferation (Ki67), indicating improved cellular integrity. In conclusion, 2% REB is a promising treatment option for PM-induced ocular surface inflammation in a rat model compared with 0.1% HA, offering the benefits of reducing inflammation, clearing pathogens, and protecting overall ocular health. Full article

Background/Objectives: The MAST kinases are ancient AGC kinases associated with many human diseases, such as cancer, diabetes, and neurodevelopmental disorders. We set out to describe the origins and diversification of MAST kinases from a structural and bioinformatic perspective to inform future research directions. Methods: We investigated MAST-lineage kinases using database and sequence analysis. We also estimate the functional consequences of disease point mutations on protein stability by integrating predictive algorithms and AlphaFold. Results: Higher-order organisms often have multiple MASTs and a single MASTL kinase. MAST proteins conserve an AGC kinase domain, a domain of unknown function 1908 (DUF), and a PDZ binding domain. D. discoideum contains MAST kinase-like proteins that exhibit a characteristic insertion within the T-loop but do not conserve DUF or PDZ domains. While the DUF domain is conserved in plants, the PDZ domain is not. The four mammalian MASTs demonstrate tissue expression heterogeneity by mRNA and protein. MAST1-4 are likely regulated by 14-3-3 proteins based on interactome data and in silico predictions. Comparative ΔΔG estimation identified that MAST1-L232P and G522E mutations are likely destabilizing. Conclusions: We conclude that MAST and MASTL kinases diverged from the primordial MAST, which likely operated in both biological niches. The number of MAST paralogs then expanded to the heterogeneous subfamily seen in mammals that are all likely regulated by 14-3-3 protein interaction. The reported pathogenic mutations in MASTs primarily represent alterations to post-translational modification topology in the DUF and kinase domains. Our report outlines a computational basis for future work in MAST kinase regulation and drug discovery. Full article

Tryptase is a tetrameric serine protease and a key component of mast cell granules. Here, we explored an integrated approach to characterize tryptase ligands, combining novel experimental binding studies using Surface Plasmon Resonance, with in silico analysis through the Exscalate platform. For this, we focused on three inhibitors previously reported in the literature, including a bivalent inhibitor and its corresponding monovalent compound. All three ligands showed concentration-dependent binding to immobilized human tryptase with the bivalent inhibitor showing the highest affinity. Furthermore, Rmax values were similar, indicating that the compounds occupy all four binding pockets of the tryptase tetramer. This hypothesis was supported by in silico computational analysis that revealed the binding mode of the monovalent ligand, one in each monomer pocket, compared with crystal structure of the bivalent one, which simultaneously occupies two binding pockets. Additionally, we solved the 2.06 Å X-ray crystal structures of human Tryptase beta-2 (hTPSB2), in both its apo form and in complex with compound #1, experimentally confirming the binding mode and the key molecular interactions predicted by docking studies for this compound. This integrated approach offers a robust framework for elucidating both the strength and mode of interaction of potential tryptase inhibitors. Full article

To achieve both safety and a lightweight design for rotary drilling rig masts, this study proposes an optimization method incorporating safety evaluation constraints. The method employs the limit state method to validate the mast structure and uses fuzzy comprehensive evaluation to quantify safety performance metrics. The optimization objective is to minimize the mast’s self-weight, with design variables defined as the geometric dimensions of key cross-sections, while imposing constraints on the strength, stiffness, stability, and safety scores. The safety score utilizes fuzzy comprehensive evaluation and a weighted aggregation method, considering indicators such as strength, stiffness, stability, and fatigue strength. An improved Salp Swarm Algorithm is utilized to execute the optimization process. Engineering case studies demonstrate that the optimized design reduces the mast’s self-weight by 6.5% under safety constraints. Compared to designs without safety constraints, the material usage increases slightly by 7.3%, but the safety performance improves by 14.74%. The findings indicate that integrating safety evaluation constraints into the optimization process not only enhances the structural safety of the mast but also achieves a favorable balance between safety and economic efficiency. This approach provides a valuable reference for the safety-focused design of rotary drilling rig masts. Full article

Integrating network pharmacological analysis and bioinformatic techniques, this study systematically investigated the molecular mechanisms of six medicinal food homologous plants (Astragalus membranaceus, Ganoderma lucidum, Dioscorea opposite, Curcuma longa, Glycyrrhiza uralensis, and Pueraria lobata) against colorectal cancer. Through screening the TCMSP database, 303 active compounds and 453 drug targets were identified. By integrating differential expression gene analysis with WGCNA on the GSE41258 dataset from the GEO database, 49 potential therapeutic targets were identified. GO and KEGG enrichment analyses demonstrated that these targets are primarily involved in drug response, fatty acid metabolism, and key cancer-related pathways. Cross-validation using three machine learning algorithms—LASSO regression, SVM-RFE, and Random Forest—pinpointed four critical target genes: CA1, CCND1, CXCL2, and EIF6. Further, CIBERSORT immune infiltration analysis revealed strong associations between these core genes and the tumor immune microenvironment in colorectal cancer patients, notably in modulating M0 macrophage infiltration and mast cell activity. Molecular docking analyses confirmed robust binding interactions between active compounds and core target proteins. This study systematically elucidated the molecular mechanisms of six medicinal food homologous plants against colorectal cancer, providing scientific evidence for their rational clinical application. Full article