ID: 38217433
Title: The use of inhibition assay in Api g 7 suspected allergy in a female patient with anaphylaxis: A case report.
Abstract: The symptoms of celery allergy are mainly presented as oral allergy symptom, but there are several case reports of patients who experienced anaphylaxis. Defensin (Api g 7), as a novel allergen in celery root, was described in 2022 r. The female patient had a history of several episodes of dyspnea and cough, associated with ingestion of spice mixes containing dried celery. Up to the point of hospitalization, there were no objective tests, either sIgE or skin prick tests, that would confirm celery sensitization. During hospitalization, patient had a positive double-blind placebo-controlled food challenge with cooked celery. The patient was sensitized to mugwort defensin Art v 1. An inhibition assay with celery allergen extract was performed to prove cross-sensitization between Art v 1 and celery allergen responsible for symptoms in the patient. In conclusion, Api g 7 is an important celery allergen that can be responsible for severe reactions. Its cross-reactivity with Art v 1 is characteristic. Negative diagnostic tests with celery do not exclude Api g 7 sensitization.

ID: 38355510
Title: Apium extract alleviates indomethacin-induced gastric ulcers in rats via modulating the VEGF and IK-κB/NF-κB p65 signaling pathway: insights from in silico and in vivo investigations.
Abstract: Gastric ulcers represent a worldwide health problem, characterized by erosions that affect the mucous membrane of the stomach and may even reach the muscular layer, leading to serious complications. Numerous natural products have been assessed as anti-ulcerogenic agents, and have been considered as new approaches for treatment or prevention of gastric ulcers. The present research investigated the preventive benefits of Apium graveolens L. (Apiaceae), known as celery, seed extract towards indomethacin-induced ulceration of the stomach in rats. Metabolomic profiling, employing liquid chromatography coupled to high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS), was implemented with the aim of investigating the chemical profile of the seeds. Histopathological analysis of gastric tissues, as well as assessment of numerous inflammatory cytokines and oxidative stress indicators, confirmed the in vivo evaluation. The prior treatment with A. graveolens seed extract resulted in a substantial reduction in the ulcer index when compared to the indomethacin group, indicating an improvement in stomach mucosal injury. Moreover, the gastroprotective effect was demonstrated through examination of the oxidative stress biomarkers which was significantly attenuated upon pre-treatment with A. graveolens seed extract. Vascular endothelial growth factor (VEGF), a fundamental angiogenic factor that stimulates angiogenesis, was markedly inhibited by indomethacin. A. graveolens seed extract restored this diminished level of VEGF. The dramatic reductions in NF-κB protein levels indicate a considerable attenuation of the indomethacin-induced IKκB/NF-κB p65 signaling cascade. These activities were also correlated to the tentatively featured secondary metabolites including, phenolic acids, coumarins and flavonoids, previously evidenced to exert potent anti-inflammatory and antioxidant activities. According to our network pharmacology study, the identified metabolites annotated 379 unique genes, among which only 17 genes were related to gastric ulcer. The PTGS2, MMP2 and PTGS1 were the top annotated genes related to gastric ulcer. The top biological pathway was the VEGF signaling pathway. A. graveolens seed extract possesses significant anti-ulcer activity, similar to famotidine, against gastric lesions induced by indomethacin in rats. It is worth highlighting that the extract overcomes the negative effects of conventional chemical anti-secretory drugs because it does not lower stomach acidity.

ID: 38763171
Title: New light on an old syndrome: Role of Api g 7 in mugwort pollen-related celery allergy.
Abstract: Celery root is known to cause severe allergic reactions in patients sensitized to mugwort pollen. We studied clinically well-characterized patients with celery allergy by IgE testing with a comprehensive panel of celery allergens to disentangle the molecular basis of what is known as the celery-mugwort syndrome. Patients with suspected food allergy to celery underwent a standardized interview. Main inclusion criteria were a positive food challenge with celery or an unambiguous case history of severe anaphylaxis. IgE to celery allergens (rApi g 1.01, rApi g 1.02, rApi g 2, rApi g 4, nApi g 5, rApi g 6, rApi g 7) and to mugwort allergens (rArt v 1, rArt v 3, rArt v 4) were determined. IgE levels ≥0.35 kUA/L were regarded positive. Seventy-nine patients with allergy to celery were included. Thirty patients had mild oral or rhinoconjunctival symptoms, and 49 had systemic reactions. Sixty-eight percent had IgE to celery extract, 80% to birch pollen, and 77% to mugwort pollen. A combination of Api g 1.01, 1.02, 4, 5, and 7 increased the diagnostic sensitivity for celery allergy to 92%. The lipid transfer proteins Api g 2 and Api g 6 were not relevant in our celery-allergic population. IgE to Api g 7, detected in 52% of patients, correlated closely (r = 0.86) to Art v 1 from mugwort pollen. Eleven of 12 patients with monosensitization to Api g 7 were IgE negative to celery extract. The odds ratio for developing a severe anaphylactic reaction rather than only mild oral symptoms was about 6 times greater (odds ratio, 5.87; 95% confidence interval, 1.08-32.0; P = .0410) for Api g 7-sensitized versus -nonsensitized subjects. There is an urgent need for routine diagnostic tests to assess sensitization to Api g 7, not only to increase test sensitivity but also to identify patients at risk of a severe allergic reaction to celery.

ID: 39670672
Title: Apium graveolens L. alleviates acute lung injury in human A-549 cells by reducing NF-κB and NLRP3 inflammasome signaling.
Abstract: Apium graveolens L. (celery) is a dietary vegetable with anti-inflammatory properties. It has the potential to treat acute lung injury (ALI) caused by COVID-19 or other diseases. To investigate the effects of Apium graveolens water extract (AGWE) on ALI in human lung A-549 cells induced by lipopolysaccharide (LPS). A-549 cells were treated with AGWE for 24 h and then stimulated with 10 μg/mL LPS for another 24 h. The effects of AGWE on cell viability, the inflammatory response, oxidative stress, and apoptosis and their regulatory factors, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling activation were analyzed. Treatment with 5-50 μg/mL AGWE reversed the decrease in cell viability caused by LPS (p < 0.05). AGWE can reduce interleukin (IL)-1β, IL-6, IL-18, and TNF-α levels; their EC50 values are 61.4, 65.7, 37.8, and 79.7 μg/mL, respectively. AGWE can reduce reactive oxygen species and thiobarbituric acid reactive substances in A-549 cells induced by LPS. AGWE also reduced the levels of apoptosis (EC50 of 74.8 μg/mL) and its regulators (Bid; Caspase-9, -8, and -3; Bax) and increased the levels of the mitochondrial membrane potential in A-549 cells induced by LPS. AGWE can also decrease the protein levels of NLRP3 and Caspase-1 and the activation of NF-κB signaling in A-549 cells induced by LPS. These results show that 10 and 50 μg/mL AGWE can reduce the acute inflammation induced by LPS by reducing NF-κB and NLRP3 inflammasome signaling and mitochondria-dependent apoptosis pathways.

ID: 39749962
Title: DL-3-N-BUTYLPHTHALIDE ALLEVIATES CARDIAC DYSFUNCTION AND INJURY POSSIBLY BY INHIBITING CELL PYROPTOSIS AND INFLAMMATION VIA THE CGAS-STING-TBK1 PATHWAY IN A PORCINE MODEL OF HEMORRHAGE-INDUCED CARDIAC ARREST.
Abstract: Introduction: Dl-3-n-butylphthalide (NBP), a small molecular compound extracted from celery seeds, has been shown to exhibit diverse pharmacological activities, including anti-inflammatory, antioxidative, and anti-apoptotic effects. Recent studies have highlighted its efficacy in treating various cardiovascular conditions, such as myocardial infarction, hypertrophy, heart failure, and cardiotoxicity. This study aimed to investigate whether NBP could alleviate cardiac dysfunction and injury following hemorrhage-induced cardiac arrest (HCA) in a porcine model and elucidate its potential mechanisms. Methods: Seventeen pigs were randomized into three groups: sham (n = 5), HCA + vehicle (n = 5), and HCA + NBP (n = 7). In the HCA + vehicle and HCA + NBP groups, the HCA model was established by continuous bleeding at a rate of 2 mL/kg/min to induce cardiac arrest. Cardiac arrest was maintained for 7 min, followed by the reinfusion of 50% of the shed blood at a rate of 5 mL/kg/min. After successful resuscitation, the HCA + NBP group received an intravenous dose of 2.5 mg/kg of NBP within 120 min. Post-resuscitation cardiac function (stroke volume, global ejection fraction) and injury biomarkers (cardiac troponin I, creatine kinase-MB) were assessed at regular intervals. At the end of the post-resuscitation observation, cardiac tissue samples were collected to assess: histopathological injury; cellular apoptosis; levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-18 (IL-18); the expression levels of NOD-like receptor pyrin domain 3 (NLRP3), caspase 1, gasdermin D (GSDMD), cyclic-GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), and tank-binding kinase 1 (TBK1); and the integrated optical density (IOD) of GSDMD N-terminal (GSDMD-N), phosphorylated STING (p-STING), and phosphorylated TBK1 (p-TBK1). Results: Following resuscitation, both stroke volume and global ejection fraction were significantly reduced, while serum levels of cardiac troponin I and creatine kinase-MB were markedly elevated in the HCA + vehicle and HCA + NBP groups compared with the sham group. However, the extent of cardiac dysfunction and injury was significantly attenuated in the HCA + NBP group relative to the HCA + vehicle group. At 24 h post-resuscitation, substantial cardiac pathological injury and apoptosis were observed. Additionally, pyroptosis-related proteins (NLRP3, caspase-1, GSDMD, GSDMD-N) were upregulated, inflammatory markers (TNF-α, IL-1β, IL-6, IL-18) were elevated, and the activation of the cGAS-STING-TBK1 pathway (cGAS, STING, TBK1, p-STING, p-TBK1) were noted in both the HCA + vehicle and HCA + NBP groups compared with the sham group. Notably, these pathological changes were significantly attenuated in the HCA + NBP group compared with the HCA + vehicle group. Conclusions: NBP provided substantial cardiac protection following HCA and resuscitation in pigs. This protective effect was likely mediated through the inhibition of cell pyroptosis and inflammation by suppressing the cGAS-STING-TBK1 signaling pathway.

ID: 40365306
Title: Dl-3-n-butylphthalide attenuates DOX-induced cardiotoxicity in mice by inhibiting Nrf2/Keap1 complex formation.
Abstract: Drug-induced cardiotoxicity (DICT), defined as myocardial injury caused by direct or indirect toxicity of therapeutic agents, disrupts cardiovascular homeostasis, underscoring the urgent need for preventive strategies in clinical practice. Doxorubicin (DOX), a clinically established anthracycline chemotherapeutic, induces dose-dependent cardiotoxicity driven by reactive oxygen species overproduction. Notably, Dl-3-n-butylphthalide (NBP), a bioactive phytochemical derived from celery, has shown potential in mitigating DOX-induced cardiomyopathy via its antioxidant activity. Therefore, this study aimed to investigate the protective effects of NBP on DOX-induced cardiomyopathy, with a focus on elucidating the underlying mechanisms. We developed both in vivo and in vitro models of DOX-induced cardiotoxicity. For the animal model, male C57BL/6 mice were administered with DOX (4 mg/kg, i.p.) once a week for 3 weeks. For the cell model, H9C2 myoblasts were exposed to 1 μM DOX for at least 6 h to establish acute cardiotoxicity. Our results demonstrate that NBP significantly improves cardiac function, as evidenced by approximately 10% increase in cardiac functional parameters (ejection fraction and left ventricular shortening fraction). Besides, NBP exerts favorable effects on cardiac inflammation, apoptosis, fibrosis, and mitochondrial damage both in vivo and in vitro. Further mechanistic investigations revealed that NBP blocks the interaction between Kelch-like ECH-associated protein-1 (Keap1) and Nrf2, thereby preventing the formation of the Nrf2/Keap1 complex. This study indicate that NBP alleviates DOX-induced cardiotoxicity by inhibiting Nrf2/Keap1 complex formation, highlighting its potential as a therapeutic agent for DICT and suggest that Nrf2/Keap1 may be a potential therapeutic target for the management of this condition.

ID: 41424259
Title: Art v 1 and Amb a 4 Co-Sensitization Identifies Italian Patients at Risk for Mugwort-Celery-Spice Syndrome.
Abstract: Pollen defensins such as Art v 1 (mugwort) and Amb a 4 (ragweed) are pivotal allergens in pollen-food syndromes, but their clinical role in Southern Europe is poorly defined. To characterize sensitization to defensins and related allergens in Italy and its association with clinical phenotypes. Between 2021 and 2025, 7176 patients underwent molecular testing in three Italian centers. Sensitization to the pollen defensins Art v 1 and Amb a 4 was evaluated, together with celery allergens representing different protein families: the PR-10 Api g 1, the nsLTPs Api g 2, Api g 6, and the defensin Api g 7 (tested in a subset). Panallergens were also assessed. Defensin sensitization occurred in 272 patients (3.8%). Art v 1 mono-sensitization (64.7%) was largely confined to respiratory disease. Dual Art v 1-Amb a 4 sensitization (30.5%) identified a distinct subgroup at high risk of food reactions (OR = 6.9; p < 0.0001). Amb a 4 sensitization followed a clear northward gradient. Among 90 patients tested for Api g 7, 82.7% were positive, all co-sensitized to Art v 1, and one-third also to Amb a 4. IgE inhibition confirmed Art v 1 as the primary sensitizer driving defensin cross-reactivity. In contrast, Api g 2 nsLTP sensitization was strongly associated with severe systemic reactions. Defensin sensitization in Italy reveals distinct molecular and geographic signatures. Isolated Art v 1 sensitization dominates and marks respiratory allergy, while co-sensitization to Amb a 4-often associated with Api g 7 co-recognition-defines patients at high risk for systemic food reactions.

ID: 42101807
Title: Unraveling the therapeutic potential of luteolin in renal pathology: a comprehensive pathway oriented approach.
Abstract: Kidney diseases, particularly chronic kidney disease (CKD), represent a significant global health challenge, affecting over 9.5% of the world’s population. Both systemic inflammation and oxidative stress are strongly associated with the development of CKD and contribute to the emergence of numerous complications. Renal injury is driven by interconnected molecular pathways that collectively exacerbate inflammation, oxidative stress, and fibrotic responses. The activation of mitogen-activated protein kinase (MAPK)/nuclear factor kappa-B (NF-κB) signaling cascades, along with NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly, synergistically amplifies the inflammatory response. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) promotes excessive generation of reactive oxygen species (ROS), whereas impairment of sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling weakens antioxidant defenses; together, these mechanisms exacerbate oxidative stress. In addition to oxidative stress, hyperglycemia also exacerbates renal damage by activating the transforming growth factor-beta (TGF-β)/hypoxia-inducible factor-1 alpha (HIF-1α) signaling axis, thereby promoting renal fibrosis. Collectively, these events culminate in progressive renal dysfunction. In addition to conventional therapies involving anti-inflammatory and antioxidant agents, emerging studies highlight the therapeutic potential of plant-derived agents in mitigating these pathological disturbances. Luteolin is a naturally occurring flavonoid abundantly distributed in a variety of dietary and medicinal plants, such as parsley, celery, green pepper, and carrots. It is predominantly found in members of the Lamiaceae, Asteraceae, Apiaceae, Fabaceae, and Poaceae families. Several studies highlight luteolin’s potential in alleviating renal diseases by targeting key mediators, including NF-κB, NLRP3, MAPK, NOX4, ROS, SIRT1, TGF-β, cytokines, and antioxidants, among others. Thus, considering the broad therapeutic potential of luteolin and the complex pathophysiology of renal diseases, the present study aims to elucidate the mechanisms through which luteolin mitigates renal injury.

ID: 42221024
Title: Structural anisotropy in celery stalks by microscopic MRI and polarized light microscopy.
Abstract: Structural anisotropy of celery stalks was studied using T 2 anisotropy in microscopic MRI (μMRI) and supplemented by quantitative polarized light microscopy (PLM) at optical resolutions. Parenchyma, which is the ground tissue in celery and has a diameter in the range of 50-90 μm, was found to have isotropic T 2; in contrast, collenchyma, which is the structural part of the ground tissue in celery and has a diameter in the range of 8-12 μm, was found to have strong anisotropic T 2. Substantial size variations within each porous structure and substantial co-existences of more than one type of structural tissues within a single μMRI voxel were noticed in the optical images, which can contribute to the less clear anisotropies in the smaller vascular structures (e.g., phloem (approximately 2-6 μm in diameter) and xylem (approximately 5-15 μm in diameter)). Celery could be used as a simple plant model to study the relationships between tissue microstructures and nuclear spin relaxation in fibrous and porous specimens.