Search Results (69)

Patients with Inflammatory Bowel Disease (IBD) exhibit a dysregulated immune response that may be further exacerbated by bioactive compounds, such as histamine. Current dietary guidelines for IBD primarily focus on symptom management and flare-up prevention, yet targeted nutritional strategies addressing histamine metabolism remain largely unexplored. This narrative review aims to summarize the existing literature on the complex interplay between IBD and histamine metabolism and propose a novel dietary framework for managing IBD progression in patients with histamine intolerance (HIT). Relevant studies were identified through a comprehensive literature search of PubMed/MEDLINE, Google Scholar, ScienceDirect, Scopus, and Web of Science. The proposed low-histamine diet (LHD) aims to reduce the overall histamine burden in the body through two primary strategies: (1) minimizing exogenous intake by limiting high-histamine and histamine-releasing foods and (2) reducing endogenous histamine production by modulating gut microbiota composition, specifically targeting histamine-producing bacteria. In parallel, identifying individuals who are histamine-intolerant and understanding the role of histamine-degrading enzymes, such as diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT), are emerging as important areas of focus. Despite growing interest in the role of histamine and mast cell activation in gut inflammation, no clinical trials have investigated the effects of a low-histamine diet in IBD populations. Therefore, future research should prioritize the implementation of LHD interventions in IBD patients to evaluate their generalizability and clinical applicability. Full article

Background: Cardiovascular disorders, especially atherosclerosis, have been associated with allergic inflammation. In addition to traditional inflammatory responses, there is evidence that the development and instability of coronary artery plaque may be influenced by effector cells of allergic inflammation. This review examines the phases of allergic pathology, the immunological mechanisms of atherosclerosis, and the clinical link between allergic diseases (asthma, atopic dermatitis, allergic rhinitis, and food allergy) and cardiovascular disease (CVD), along with future therapeutic perspectives. Material and Method: A literature search was conducted in PubMed, Google scholar; ScienceDirect, Scopus, and studies published between 2014–2024 were taken into consideration. Keywords included allergic inflammation, eosinophils, mast cells, reactive oxygen species, atherosclerosis, Th2 cells, and cytokines. Epidemiological studies and review articles were included. Results: Emerging evidence suggests that allergic inflammation contributes to atherosclerosis through interconnected mechanisms such as eosinophil activation, reactive oxygen species production, mast cell degranulation, and endothelial dysfunction. Th2-driven immune responses, which are mediated by cytokines such as IL-4, IL-5, and IL-13, as well as eosinophil activity and mast cell degranulation, play a crucial role in vascular inflammation and plaque progression. Additionally, changes in lipid metabolism contribute to this process. Epidemiological studies support this connection, indicating that patients with chronic allergic conditions such as asthma, allergic rhinitis, food allergy, and atopic dermatitis experience increased cardiovascular morbidity. However, most current data are observational, and our understanding of the underlying mechanisms in humans remains limited, often relying on insights gained from preclinical models. Conclusions: A potential mechanism for cardiovascular risk is suggested by the interaction between atherosclerosis and allergic inflammation. Promising alternatives for treating allergic inflammation and cardiovascular issues include novel treatments like cytokine inhibitors, mast cell stabilizers, and biologics that target certain pathways. Further research is necessary to see whether concentrating on allergy pathways could lead to innovative treatments for cardiovascular disorders or vice versa. Full article

Background and Aims: Metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), involves inflammation, fibrosis, steatosis, and oxidative stress. Previous research from our lab shows that cannabigerol (CBG) reduces inflammation and fibrosis in male MASH mice, but its effects in females remain unknown. Given immune cell population changes in MASLD patients, this study examines CBG’s impact on methionine-choline deficient (MCD) diet-induced MASH in female mice. Methods: MCD-fed female mice are supplemented with two different doses for three weeks. Liver fibrosis, steatosis, oxidative stress, ductular reaction, and inflammation are assessed via Sirius Red, Oil Red O, immunohistochemistry, and immunofluorescence staining. Immune cell changes in non-parenchymal cells (NPCs) are analyzed via flow cytometry. Results: CBG treatment improves liver health by reducing leukocyte infiltration. Both CBG doses significantly decrease fibrosis, oxidative stress, ductular proliferation, and inflammation in MCD-fed mice, including monocyte and T lymphocyte reductions. Additionally, CBG downregulates mast cell activation, inhibiting transforming growth factor (TGF)-β1 release, thereby suppressing hepatic stellate cell activation. This reduces collagen deposition, fibrosis, and ductular proliferation. Conclusions: Our findings provide insights for pre-clinical and clinical research, highlighting CBG’s potential therapeutic role and dosage considerations in mitigating liver fibrosis and inflammation in female patients. Full article

Introduction: Migraine is a prevalent neurological disorder characterized by recurrent headaches with autonomic and neurological symptoms, significantly impacting quality of life globally. Its pathogenesis involves genetic, neurological, inflammatory, and metabolic factors, with insulin resistance and metabolic dysfunction increasingly recognized as important contributors. Historically, it has been known that certain foods can trigger migraine attacks, which led for many years to the recommendation of elimination diets—now understood to primarily target histamine-rich foods. Over the past two decades, attention has shifted toward underlying metabolic disturbances, leading to the development of dietary approaches specifically aimed at addressing these dysfunctions. Methods: A scoping literature review was conducted using PubMed and Embase to evaluate the relationships among migraine, insulin-related mechanisms, neurogenic inflammation, and dietary interventions. Initial searches focused on “MIGRAINE AND (neurogenic inflammation)” (2019–15 April 2025), followed by expanded searches from 1950 onward using terms such as “MIGRAINE AND (insulin, insulin resistance, hyperinsulinism)”, and “MIGRAINE AND (diet, dietary, nutrition, nutritional)”. A specific search also targeted “(INSULIN OR insulin resistance OR hyperinsulinism) AND (neurogenic inflammation)”. Abstracts were screened, full texts were retrieved, and duplicates or irrelevant publications were excluded. No filters were applied by article type or language. Systematic reviews and meta-analyses were prioritized when available. Results: Migraine pathogenesis involves trigeminovascular system activation, neurogenic inflammation mediated by CGRP and PACAP, immune dysregulation, mast cell activation, and cortical spreading depression (CSD). Emerging evidence highlights significant associations between migraine, insulin resistance, and hyperinsulinism. Hyperinsulinism contributes to migraine through TRPV1 sensitization, increased CGRP release, oxidative stress, mitochondrial dysfunction, and systemic inflammation. Metabolic dysfunction, including obesity and insulin resistance, exacerbates migraine severity and frequency. Dietary interventions, particularly anti-inflammatory, Mediterranean, and ketogenic diets, show promise in reducing migraine frequency and severity through mechanisms involving reduced inflammation, oxidative stress, improved mitochondrial function, and glucose metabolism stabilization. Conclusions: The interplay between insulin resistance, metabolic dysfunction, and neuroinflammation is crucial in migraine pathophysiology. Targeted dietary interventions, including ketogenic and Mediterranean diets, demonstrate significant potential in managing migraines, emphasizing the need for personalized nutritional strategies to optimize therapeutic outcomes. Full article

Cassava is a tropical tuberous root crop, feeding over a billion people globally. However, research on the chemical composition and bioactive effects of cassava leaves remains scarce. Two specific varieties of South China No. 9 (green leaves (G.L.)) and South China No. 20 (purple leaves (P.L.)) were investigated in this study. The components of G.L. and P.L. were analyzed under different extraction methods using ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Results showed that cassava leaf extracts are rich in bioactive metabolites such as D-(+)-mannose, trigonelline, rutin, kaempferol-3-O-rutinoside, and oleamide. To assess the anti-inflammatory efficacy of bioactive compounds, animal models were established. Compared to the histamine group (NA), the group treated with the extracts had reduced epidermal thickness in hematoxylin and eosin (HE) staining. Further analysis revealed a drastic reduction in the number of mast cells in toluidine blue (TB) staining and expression levels of inflammatory cytokines (IL-17 and TNF-α) in immunohistochemistry (IHC) staining. The ethanolic extracts from the leaves demonstrated potent anti-inflammatory activities, with the extract from G.L. surpassing that from P.L. Transcriptomic analyses propose that the anti-inflammatory effects of cassava leaves may be related to the modulation of genes involved in mast cell activation, such as Cma1, Cpa3, and Fn1, among others. Network pharmacology unveiled that the extract of cassava leaves modulates pathways associated with apoptosis, inflammation, and metabolism. Molecular docking revealed strong binding interactions between 1-stearoylglycerol and oleamide from cassava leaves extracts and the proteins of AKT1, TNF, and BRAF. Overall, cassava leaf extracts seem to be a promising natural anti-inflammatory agent. Full article

Skin photoageing remains a topic of considerable concern. Retinol (RT) and retinyl palmitate (RP) have shown preliminary therapeutic efficacy; nevertheless, the high irritation associated with RT and the relatively modest efficacy of RP have constrained their broader application. Consequently, this study explored the effects and biosafety of RT and RP in repairing UV-induced skin ageing through a series of in vitro cell experiments, in vitro hemolysis assays, UV-irradiated mouse models, and molecular simulation techniques. The findings revealed that the interaction between RT and RP achieved complementary and enhanced therapeutic outcomes. Specifically, this combination improved the biosafety profile of retinoid formulations, accelerated cell migration rates, and facilitated the activation of the peroxisome proliferator-activated receptor α (PPARα) pathway. Moreover, the action of RT and RP further mitigated epidermal hyperplasia, mast cell infiltration, and the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α), while stimulating the synthesis of type I collagen. Metabolomics and transcriptomics analyses indicated that RT and RP exerted complementary effects through metabolic pathways, significantly elevating the overall therapeutic efficacy. Network pharmacology and molecular docking studies unveiled that the structural similarity between RT and RP was one of the contributors to their enhancement. In conclusion, this study demonstrated that the combined application of RT and RP exhibited marked effects. Through their mutual action, they not only potentiated each other’s therapeutic effects but also achieved complementary and optimised therapeutic outcomes, thereby substantially enhancing the overall efficacy. Full article

Background/Objectives: Symptoms of pudendal nerve neuropathy may overlap with various symptoms of interstitial cystitis (IC). As documented, there is a well-established correlation between the genes involved in ATP metabolism, neuropathy, and IC. ATP-binding cassette (ABC) transporters genes, in fact, are vital for ATP signaling. This study aims to associate the ABCF2 gene with a suspected pudendal nerve neuropathy and IC. Methods: Histological analysis was conducted for diagnosing IC while the genetic variant was identified by whole exome sequencing (WES) Trio and confirmed through Sanger. Results: We report a patient with IC, confirmed by histological examination, presenting with a suspected bladder and pudendal nerve neuropathy, though not analytically confirmed. Histological analysis revealed urothelial detachment caused by a dense subepithelial lymphocytic infiltrate, predominantly composed of mast cells, which serve as key diagnostic markers for interstitial cystitis (IC). WES analysis identified the heterozygous genetic variant c.1253T>G p.Phe418Cys within ABCF2 gene, precisely in its functional domain which actively operates in the hydrolysis of ATP energizing various biological systems. As reported, this gene displays high expression patterns in bladder tissue. The variant, absent in the healthy brother, was inherited from the father which presents mosaicism. The in silico prediction analyses classified this variant as pathogenic, identifying potential alterations in the protein structure. Conclusions: Although the precise role of ABCF2 should be supported by further studies, we hypothesize that its disruption might impair ATP metabolism, likely altering the nociceptive response and leading to the patient’s neuropathy. Further analyses are imperative to validate this research, for laying the groundwork for a specific therapy targeting the genetic dysregulation involved in this condition. Full article

Many polyunsaturated fatty acids within cells exhibit diverse physiological functions. Particularly, arachidonic acid is the precursor of highly bioactive prostaglandins and leukotrienes, which are pro-inflammatory mediators. However, polyunsaturated fatty acids, such as arachidonic, docosahexaenoic, and eicosapentaenoic acids, can be metabolized into specialized proresolving mediators (SPMs), which have anti-inflammatory properties. Given that pro-inflammatory mediators and SPMs are produced via similar enzymatic pathways, SPMs can play a crucial role in mitigating excessive tissue damage induced by inflammation. Mast cells are immune cells that are widely distributed and strategically positioned at interfaces with the external environment, such as the skin and mucosa. As immune system sentinels, they respond to harmful pathogens and foreign substances. Upon activation, mast cells release various pro-inflammatory mediators, initiating an inflammatory response. Furthermore, these cells secrete factors that promote tissue repair and inhibit inflammation. This dual function positions mast cells as central regulators, balancing between the body’s defense mechanisms and the need to minimize tissue injury. This review investigates the production of SPMs by mast cells and their subsequent effects on these cells. By elucidating the intricate relationship between mast cells and SPMs, this review aims to provide a comprehensive understanding of the mechanism by which these cells regulate the delicate balance between tissue damage and repair at inflammatory sites, ultimately contributing to the resolution of inflammatory responses. 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

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous tumor, and distinguishing its subtypes holds significant value for diagnosis, treatment, and the prognosis. Methods: Unsupervised clustering analysis was conducted to classify HCC subtypes. Subtype signature genes were identified using LASSO, SVM, and logistic regression. Survival-related genes were identified using Cox regression, and their expression and function were validated via qPCR and gene interference. GO, KEGG, GSVA, and GSEA were used to determine enriched signaling pathways. ESTIMATE and CIBERSORT were used to calculate the stromal score, tumor purity, and immune cell infiltration. TIDE was employed to predict the patient response to immunotherapy. Finally, drug sensitivity was analyzed using the oncoPredict algorithm. Results: Two HCC subtypes with different gene expression profiles were identified, where subtype S1 exhibited a significantly shorter survival time. A subtype scoring formula and a nomogram were constructed, both of which showed an excellent predictive performance. COL11A1 and ACTL8 were identified as survival-related genes among the signature genes, and the downregulation of COL11A1 could suppress the invasion and migration of HepG2 cells. Subtype S1 was characterized by the upregulation of pathways related to collagen and the extracellular matrix, as well as downregulation associated with the xenobiotic metabolic process and fatty acid degradation. Subtype S1 showed higher stromal scores, immune scores, and ESTIMATE scores and infiltration of macrophages M0 and plasma cells, as well as lower tumor purity and infiltration of NK cells (resting/activated) and resting mast cells. Subtype S2 was more likely to benefit from immunotherapy. Subtype S1 appeared to be more sensitive to BMS-754807, JQ1, and Axitinib, while subtype S2 was more sensitive to SB505124, Pevonedistat, and Tamoxifen. Conclusions: HCC patients can be classified into two subtypes based on their gene expression profiles, which exhibit distinctions in terms of signaling pathways, the immune microenvironment, and drug sensitivity. Full article

Allergic rhinitis affects millions globally, causing significant discomfort and reducing the quality of life. This study investigates the metabolic alterations in murine mast cells (MC/9) under allergic rhinitis conditions induced by lipopolysaccharide (LPS) stimulation, employing UHPLC-QTOF-MS-based untargeted and targeted metabolomics. The analysis identified 44 significantly regulated metabolites, including histamine, leukotrienes, prostaglandins, thromboxanes, and ceramides. Key metabolic pathways such as arachidonic acid, histidine, and sphingolipid metabolisms were notably modulated. The study further examined the therapeutic effects of triprolidine and zileuton, demonstrating their capacity to reverse LPS-induced metabolic shifts. Triprolidine primarily modulated histidine and sphingolipid metabolism, while zileuton targeted arachidonic acid and sphingolipid metabolism. These findings underscore the utility of metabolomics analysis in elucidating the complex biochemical pathways involved in allergic rhinitis and highlight the potential of metabolomics for evaluating therapeutic interventions. This study enhances our understanding of mast cell metabolism in allergic responses and provides a robust model for assessing the efficacy of anti-allergic agents, paving the way for more effective treatments. Full article

The mortality rate of ovarian cancer (OC) remains the highest among female gynecological malignancies. Advanced age is the highest risk factor for OC development and progression, yet little is known about the role of the aged tumor microenvironment (TME). We conducted RNA sequencing and lipidomic analysis of young and aged gonadal adipose tissue from rat xenografts before and after OC formation. The rates of tumor formation (p = 0.047) and tumor volume (p = 0.002) were significantly higher in the aged rats than in their young counterparts. RNA sequencing data showed significant differences in gene expression profiles between the groups of young and aged rat adipose tissues (p < 0.05), including S100a8, S100a9, Il1rl1, Lcn2, C3, Hba-a1, Fcna, and Pnpla3. At the time of tumor generation, there were also changes in the lipid components within the gonadal adipose tissues of young and aged rats, with higher levels of free fatty acids (FFAs) and triglycerides (TGs) in aged rats. Furthermore, the aged TME showed changes in immune cell composition, especially inflammation-related cells, including neutrophils, myeloid dendritic cells, CD4+ T cells (non-regulatory), and mast cell activation (p < 0.05). The correlation between S100a8, S100a9, neutrophil, and omega-5, FFA 18:3 levels was also determined. Additionally, omega-5, which is downregulated in aged rats, inhibited OC cell proliferation in vitro (p < 0.001). Our study suggests that the aged TME promotes OC proliferation resulting from age-related changes in gene/pathway expression, lipid metabolism, and immune cell distribution. Targeting the aging adipose microenvironment, particularly lipid metabolism, is a promising therapeutic strategy for OC and warrants further investigation. Significance: The aging microenvironment contributes to OC development and progression because of changes in the immune response regulatory genes S100a8 and S100a9, secreted by adipocytes, preadipocytes, or neutrophils, and by altering omega-5 metabolism. Full article

Mycosporine-glycine (M-Gly), a member of the mycosporine-like amino acid (MAA) family, is known for its potent antioxidant and anti-inflammatory properties. However, its in vivo efficacy in alleviating acute skin photodamage, primarily caused by oxidative stress, has not been well explored. In this investigation, 30 female ICR mice were divided into four groups: a control group and three Ultraviolet B (UVB)-exposed groups treated with saline or M-Gly via intraperitoneal injection for 30 days. At the end of the experiment, UVB exposure caused erythema, wrinkling, collagen degradation, and mast cell infiltration in mouse dorsal skin. M-Gly treatment improved skin appearance and reduced mast cell numbers, while also elevating antioxidant levels, including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Furthermore, M-Gly reduced inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β, typically upregulated after UVB exposure. M-Gly also protected skin collagen by upregulating type I procollagen and decreasing MMP-1 levels. Skin metabolomic profiling identified 34 differentially abundant metabolites, and transcriptomic analysis revealed 752 differentially expressed genes. The combined metabolomic and transcriptomic data indicate that M-Gly’s protective effects may involve the regulation of ion transport, cellular repair, metabolic stability, collagen preservation, and the Nrf2/HO-1 pathway. These findings highlight M-Gly’s potential as an endogenous antioxidant for protecting skin from UVB-induced damage. Full article

Background/Objectives: Allergic contact dermatitis (ACD), an inflammatory skin condition, is commonly treated with topical corticosteroids; however, long-term use of these drugs is associated with various risks, such as skin atrophy and steroid resistance. Triacetin (TA), a triglyceride metabolized to acetate, exerts anti-inflammatory affects by activating AMP-activated protein kinase (AMPK) and suppressing mast cell degranulation. Here, we aimed to assess the immediate and long-term effects of TA on ACD suppression, focusing on AMPK activation, using a 2,4-dinitrofluorobenzene-induced rodent model. Methods: Various concentrations of TA were topically applied to rats with 2,4-dinitrofluorobenzene-induced dermatitis. Ear thickness was measured, and histological analysis was performed to assess the inflammation, mast cell infiltration, and degranulation in the established models. AMPK activation was analyzed via Western blotting, and TA degradation was assessed via gas chromatography-mass spectrometry. Dorsomorphin (an AMPK inhibitor) was used to evaluate the effects of AMPK on ACD. Results: TA significantly inhibited inflammation and mast cell degranulation in a dose-dependent manner, with 0.25 mmol/L showing the most potent effects. It also activated AMPK activation. Notably, AMPK inhibition reversed the effects of TA. Conclusions: Overall, TA exerted immediate and long-term anti-inflammatory effects via AMPK activation and inhibition of mast cell degranulation, showing potential as a non-steroidal therapeutic for ACD. Full article

Mast cell tumors (MCTs) are common skin neoplasms in dogs. Prognostic indicators include histologic grade, clinical stage, high Ki-67 index, elevated argyrophilic nucleolus organizer regions (AgNOR) index, c-kit mutations, and recurrence after surgery. Blood serum redox status has been shown to correlate with prognostic factors in canine lymphoma and mammary tumors. This study aimed to assess the correlation between established prognostic factors and serum redox status and lipid metabolism analytes in dogs with MCTs. Dogs with cutaneous (n = 33) or subcutaneous (n = 6) MCTs, without comorbidities, were studied. Staging was evaluated based on cytology of regional lymph nodes and ultrasound-guided liver and spleen aspiration cytology. Histologic grading and immunohistochemical staining for Ki-67 and KIT patterns were performed on excised tumor specimens. Dogs were categorized by Patnaik grading (1–3), Kiupel grading (low/high), metastatic status, Ki-67 positive nuclei per cm² (>23 or ≤23), and KIT pattern (I, II–III). Paraoxonase-1, Butyrylcholinesterase, Cupric Reducing Antioxidant Capacity (CUPRAC), Diacron Reactive Oxygen Metabolites (d-ROMs), and oxy-adsorbent levels were measured before any therapeutic intervention. ANOVA and independent t-tests were used to detect differences in the mean values among groups. Paraoxonase-1 activity was significantly lower in Patnaik grade 3 (p = 0.003) and Kiupel high-grade (p = 0.022) MCTs. No significant differences were found in CUPRAC, d-ROMs, or oxy-adsorbent levels across different prognostic groups. This study found a significant correlation between histologic grading and Paraoxonase-1 activity, suggesting a potential role of Paraoxonase-1 as a prognostic biomarker in canine MCTs. Full article