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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2025 · IF 6.2

Molecular Mechanism of Glycation Structure-Mediated Immune Recognition and Sensitization by Typical Milk Allergens

Qiaozhi Zhang,Youliang Song,Yuhao Jiang,Aiqian Ye,Zhongshan Gao,Kan Jiang,Linglin Fu

This study examines how α-dicarbonyl compounds─methylglyoxal (MGO) and glyoxal (GO)─affect the structure and allergenicity of β-lactoglobulin (β-LG) and α-casein (α-CN) during thermal processing. Glycation-induced changes were analyzed using SDS-PAGE, circular dichroism, and HPLC-MS/MS, while advanced glycation end-products (AGEs) were quantified via UHPLC-QqQ-MS/MS. Results showed that GO was more reactive than MGO, modifying Lys/Arg residues and increasing AGEs in a temperature- and concentration-dependent manner. Glycation reduced the IgE-binding capacity of β-LG but enhanced that of α-CN. In vitro studies revealed that glycated β-LG disrupted Caco-2 monolayer integrity and was more efficiently internalized by bone marrow-derived dendritic cells (BMDCs), upregulating costimulatory factors including CD80, CD86, and CD103. Transcriptomic analysis of monocyte-derived dendritic cells linked glycated β-LG to IL-17, the Toll-like receptor, and NF-κB pathways. Further pathway inhibition experiments demonstrated that the TLR4/NF-κB axis is an important contributor to BMDC maturation and inflammatory cytokine production induced by glycated β-LG. These findings demonstrate that MGO and GO alter the conformational structures and IgE-binding epitopes of milk allergens during heating, differentially modulating their allergenicity. This study provides mechanistic insights into how thermal processing affects the allergenic properties of food allergens, offering new strategies for food safety evaluation and allergy control.

研究领域: 食物过敏 · 分子免疫学 · 食品化学 · 结构生物学 · 细胞生物学 · 分子机制
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF FOOD BIOCHEMISTRY · 2019 ·Vol. 44 ·期 2 ·e13113 · IF 1.358

Double enzyme hydrolysis for producing antioxidant peptide from egg white: Optimization, evaluation, and potential allergenicity

Jin Yuan,Ying Zheng,Yong Wu,Hongbing Chen,Ping Tong,Jinyan Gao

Egg white is a good source of high-quality proteins in food products and an excellent source of antioxidant active peptides through hydrolysis. The hydrolysis conditions for the preparation of potent antioxidant peptides from egg white with chymotrypsin and pepsin were optimized by the response surface methodology. The antioxidant activity and potential allergenicity of the prepared peptides were evaluated by the oxidative damage model and IgE-binding capability, respectively. After ultrafiltration, the peptide produced using the optimized parameters (preheating time of 3.16 hr, hydrolysis time of 3 hr, a sample/solution ratio of 10%, multiple enzymes ratio ( E 1/ E 2) of 1.7:1, and E/S of 0.4%) showed antioxidant activity of was 30.86 μmol AAE/g DW and with low potential for allergenicity. The optimized method is efficient and economical and may be applied to the industrial production of antioxidant peptides to obtain nutraceutical and pharmaceutical agents with low sensitivity. However, further in vivo studies must be conducted. Practical applications Egg is consumed as an excellent source of protein. Antioxidant peptides released from egg white is considered to be used in food preservation and human health. Few researches on the optimization of egg peptides were aimed to obtain practical techniques used in the food industry. In this paper, egg white hydrolysis peptide with high antioxidant property and low potential allergenicity was prepared after the optimization of double enzyme hydrolysis. The products could be a natural health care products derived from a dietary source and considered using in additive during food production and health food. And the methods used are economical and energy-saving and could be developed to utilize in the food industry.

研究领域: 食品科学 · 生物化学 · 营养学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Advanced Science · 2021 ·Vol. 9 ·期 3 ·2102460 · IF 16.806

Fine Particulate Matter Induces Childhood Asthma Attacks via Extracellular Vesicle-Packaged Let-7i-5p-Mediated Modulation of the MAPK Signaling Pathway

Rui Zheng,Mulong Du,Man Tian,Zhaozhong Zhu,Chengcheng Wei,Haiyan Chu,Cong Gan,Jiayuan Liang,Renjie Xue,Fang Gao,Zhenguang Mao,Meilin Wang,Zhengdong Zhang

Fine particulate matter less than 2.5 µm in diameter (PM 2.5 ) is a major risk factor for acute asthma attacks in children. However, the biological mechanism underlying this association remains unclear. In the present study, PM 2.5 -treated HBE cells-secreted extracellular vesicles (PM 2.5 -EVs) caused cytotoxicity in “horizontal” HBE cells and increased the contractility of “longitudinal” sensitive human bronchial smooth muscle cells (HBSMCs). RNA sequencing showed that let-7i-5p is significantly overexpressed in PM 2.5 -EVs and asthmatic plasma; additionally, its level is correlated with PM 2.5 exposure in children with asthma. The combination of EV-packaged let-7i-5p and the traditional clinical biomarker IgE exhibits the best diagnostic performance (area under the curve [AUC] = 0.855, 95% CI = 0.786–0.923). Mechanistically, let-7i-5p is packaged into PM 2.5 -EVs by interacting with ELAVL1 and internalized by both “horizontal” recipient HBE cells and “longitudinal” recipient-sensitive HBSMCs, with subsequent activation of the MAPK signaling pathway via suppression of its target DUSP1 . Furthermore, an injection of EV-packaged let-7i-5p into PM 2.5 -treated juvenile mice aggravated asthma symptoms. This comprehensive study deciphered the remodeling of the extracellular environment mediated by the secretion of let-7i-5p-enriched EVs during PM 2.5 -induced asthma attacks and identified plasma EV-packaged let-7i-5p as a novel predictor of childhood asthma.

CAS / MDL: 21645-51-2
研究领域: 环境健康 · 分子生物学 · 呼吸医学 · 细胞生物学 · 临床诊断
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Scientific Reports · 2024 ·Vol. 14 ·期 1 ·1-12 · IF 3.8

Serum metabolomics analysis reveals potential biomarkers of penicillins-induced fatal anaphylactic shock in rats

Shi Qianwen,Wang Shuhui,Wang Gege,Wang Tao,Du Kaili,Gao Cairong,Guo Xiangjie,Fu Shanlin,Yun Keming

Immunoglobulin E (IgE)-mediated immediate hypersensitivity reactions are the most concerning adverse events after penicillin antibiotics (PENs) administration because of their rapid progression and potential for fatal outcome. However, the diagnosis of allergic death is a forensic challenge because it mainly depends on nonspecific characteristic morphological changes, as well as exclusion and circumstantial evidence. In this study, an untargeted metabolomics approach based on liquid chromatography-mass spectrometry (LC-MS) was used to screen potential forensic biomarkers of fatal anaphylactic shock induced by four PENs (benzylpenicillin (BP), amoxicillin (AMX), oxacillin (OXA), and mezlocillin (MEZ)), and analyzed the metabolites, metabolic pathway and the mechanism which were closely related to the allergic reactions. The metabolomics results discovered that a total of 24 different metabolites in all four anaphylactic death (AD) groups, seven of which were common metabolites. A biomarker model consisting of six common metabolites (linoleic acid, prostaglandin D2, lysophosphatidylcholine (18:0), N-acetylhistamine, citric acid and indolelactic acid) AUC value of Receiver Operating Characteristic (ROC) curve was 0.978. Metabolism pathway analysis revealed that the pathogenesis of PENs-induced AD is closely related to linoleic acid metabolism. Our results revealed that the metabolomic profiling has potential in PENs-induced AD post-mortem diagnosis and metabolic mechanism investigations.

CAS / MDL: 103616-89-3
研究领域: 药理学 · 毒理学 · 法医学 · 代谢组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CLINICAL AND EXPERIMENTAL ALLERGY · 2021 ·Vol. 52 ·期 1 ·46-58 · IF 5.018

Substance P-induced lung inflammation in mice is mast cell dependent

Nan Wang,Jue Wang,Yongjing Zhang,Shiling Hu,Tianxiao Zhang,Yuanyuan Wu,Xiuzhen Sun,Tao Zhang,Shuanying Yang,Langchong He

Background Allergic asthma is a common inflammatory lung disease and a major health problem worldwide. Mast cells (MCs) play a key role in the early-stage pathophysiology of allergic asthma. Substance P (SP) functions in neurogenic inflammation by activating MCs, and therefore, it may to participate in the occurrence and development of asthma. Objective We examined the relationship between SP and lung inflammation, and also whether SP can directly trigger asthma. Methods We measured the number of peripheral blood eosinophils, neutrophils and basophils and evaluated the levels of IgE and SP in blood samples of 86 individuals with allergic asthma. Serum IgE and SP levels were also determined in 29 healthy individuals. C57BL/6 mice were subjected to different doses of SP, and bronchoalveolar lavage fluid (BALF) was collected to count the inflammatory cells. Lung tissues were analysed using histopathological methods to evaluate lung peribronchial inflammation, fibrosis and glycogen deposition. Levels of IgE, interleukin (IL)-1, IL-2, IL-4, IL-5, IL-13, IL-17 and IFN-γ were determined in mouse serum. Results Substance P levels were increased in the serum samples of patients with asthma. SP induced mouse lung peribronchial inflammation, fibrosis and glycogen deposition, with high levels of Th2-related cytokines such as IL-4, IL-5 and IL-13 observed in the BALF. Furthermore, low level of total IgE was noted in the serum, and SP had little effect on MC-deficient kit W-sh/W-sh mice. Conclusions & clinical relevance Substance P levels increased significantly in serum of asthmatic patients and independently associated with the risk of asthma. Furthermore, SP induced Th2 lung inflammation in mice, which was dependent on MCs. Graphical Here, we found that SP levels were increased in the serum samples of patients with asthma, which was independently associated with the risk of asthma. In mice model, SP induced lung peribronchial inflammation, fibrosis, and glycogen deposition, with high levels of Th2-related cytokines in the BALF. Furthermore, low level of total IgE was noted in the serum, and SP had little effect on MC-deficient kit W-sh/W-sh mice, which indicated that SP induced Th2 lung inflammation in mice was dependent on MCs.

CAS / MDL: 148470-19-3
研究领域: 免疫学 · 肺科学 · 过敏学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD RESEARCH INTERNATIONAL · 2025 · IF 8

Ultrasonic regulation of β-lactoglobulin/puerarin complex: structural modification, digestive properties, and allergenicity suppression through controlled polyphenol interactions

Peng Man,Jinghua Pei,Sijia Chen,Xiue Han,Huajiang Zhang

This study explored the effects of ultrasound on β-lactoglobulin (β-LG)/puerarin (PUE) complexes, focusing on structural, digestive, and allergenic properties. Molecular simulations revealed hydrogen bonding as the primary interaction between PUE and β-LG. Ultrasound reduced β-LG crystallinity (via XRD), further enhanced by PUE encapsulation. Moderate ultrasound (300 W) increased thermal denaturation temperature by 8.2 °C (DSC) and enhanced digestibility to 78.3 ± 1.2 % (vs. 62.5 ± 2.1 % in untreated group), while excessive power (500 W) caused structural damage. Ultrasonic treatment increased the β-sheet content of β-LG, led to a reorganization of its tertiary structure. Allergenicity assays demonstrated significant reductions in IgE and IgG binding capacity for 300 W-treated complexes. These findings highlighted moderate ultrasound (300 W) as an effective strategy to modulate functionality and reduce allergenicity in protein-polyphenol colloids, offered insights for food science applications.

CAS / MDL: 7647-14-5
研究领域: 食品科学 · 超声学 · 蛋白质化学 · 生物化学 · 致敏性研究 · 分子模拟 · 消化生理学
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FOOD CHEMISTRY · 2025 · IF 9.8

Investigation of α-dicarbonyl compounds induced glycation on the digestive stability of shrimp tropomyosin and intestinal microbiota

Lichun Liu,Ziye Zhang,Wei Yang,Fatih Özogul,Zhenxing Li,Hong Lin

α-dicarbonyl compounds are widely present in foods, while their modification effects on food allergens are unclear. This work was conducted to investigate the effects of α-dicarbonyl compounds (glyoxal (GO), methylglyoxal (MGO) and 2, 3-butanedione (BU)) on the digestive stability and intestinal flora of shrimp tropomyosin (TM). As the results, higher α-dicarbonyl concentration, longer time and higher temperature could exacerbate the modification of TM. Compared with TM, GO and MGO significantly reduced the digestive resistance of TM and the IgG-binding capacity of AGEs-TM digests. Although in vitro digestion reduced IgE-binding capacity of TM/AGEs-TM, in vivo evidence (intestinal biopsy and gut microbiota) suggested that they still elicits immune responses. In addition, AGEs-TM could reduce the richness and diversity of intestinal flora, increase the abundance of inflammation-related flora and flora imbalance index, which could provide a new insight into the effects of AGEs on the digestive stability of shrimp tropomyosin and intestinal microbiota.

研究领域: 食品化学 · 过敏学 · 分子生物学 · 营养科学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Immunology · 2024 · IF 5.7

Neutrophil-activating protein in Bacillus spores inhibits casein allergy via TLR2 signaling

Zhuwei Liang,Chao Zhang,Xiaoyu Liu,Kaiyue Yang,Zhile Xiong,Bingshao Liang,Jialiang Mai,Xiaojun Xiao,Jie Liu,Pingchang Yang,Damo Xu,Zhenwen Zhou

Background: Milk allergy commonly occurs in children, mainly caused by bovine-derived casein (CAS) protein. Neutrophil-activating protein (NAP) of Helicobacter pylori plays an immunomodulatory role with potential to suppress Th2-type immune responses. Bacillus subtilis (B. subtilis) spores are commonly used as oral vectors for drug delivery.Objective: To investigate whether recombinantly expressed NAP on B. subtilis spores could be an effective treatment for CAS allergy in mouse.Methods: After CAS sensitization, mice were orally administered B. subtilis spores expressing recombinant NAP for 6 weeks. Allergic symptoms and parameters were evaluated after CAS challenge oral gavage, including allergic inflammation, splenic cytokines, and serum-specific antibodies. Protein levels of Toll-like receptor 2 (TLR2) and c-JUN in the jejunum tissue were measured by western blot. Bone marrow-derived macrophages (BMDMs) were stimulated with inactivated NAP spores to measure the influence on cytokine profiles in vitro.Results: NAP recombinant spore treatment significantly reduced allergic symptoms and intestinal inflammation. Interleukin-12 and interferon-gamma levels increased, whereas serum CAS-specific IgG1 and IgE levels decreased. TLR2 and c-JUN expression levels were elevated in the jejunal tissue. Inactivated NAP spores polarized BMDMs to the M1 phenotype and enhanced cytokine expression, which were inhibited by a TLR2 neutralizing antibody.Conclusion: NAP offers a new strategy in the treatment of CAS allergy by inhibiting the Th2 response, while eliciting macrophages to promote Th1 immune responses.

CAS / MDL: 144-55-8
研究领域: 免疫学 · 过敏 · 微生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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LWT-FOOD SCIENCE AND TECHNOLOGY · 2025 · IF 6.6

The insight into the Maillard reaction of β-lactoglobulin and chitosan with different molecular weights, and the evaluation of desensitization effects

Xiaoning Zhang,Haiyan Cong,Yu Sun,Haohui Li,Baoer Zuo,Meifeng Li,Sining Li,Mingyi Wang

The covalent conjugation of chitosan to β-lactoglobulin (βLg) via Maillard reaction alters its structure and characteristics, providing a method to reduce allergenicity. The molecular weight (Mw) of chitosan plays a crucial role in the conjugation process, which in turn affects the desensitization effectiveness to βLg. The degree of conjugation decreased from 46.4 % ± 2.6 % (βC-1 ) to 27.6 % ± 2.9 % (βC-100) as the Mw increased from 1 kDa to 100 kDa. Notably, βC-1 showed a significant reduction in β-sheet content, resulting in a greater increase in surface hydrophobicity and improved thermostability compared to βC-10 and βC-100. Consequently, βC-1 demonstrated the most effective desensitization, with the highest inhibition of immunoglobulin E (IgE) combining capacity and the best suppression of cytokine overproduction in KU812 cells. Additionally, the overexpression of IgE and inflammatory factors in mice was significantly suppressed after βLg was conjugated with chitosan, alleviating dysbiosis of gut microbiota at both phyla and family levels and lessening anaphylactic response to βLg. The desensitization effects were observed in the order of βC-1 > βC-10 > βC-100.

CAS / MDL: 8049-47-6 8008-63-7
研究领域: 食品科学 · 过敏学 · 糖化学 · 免疫学 · 分子营养学
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Biochemistry and Cell Biology · 2022 ·Vol. 101 ·期 1 · IF 3.73

2-Undecanone alleviates asthma by inhibiting NF-κB pathway

Guihua Song,Suping Yu,Yan Zhang,Mengmeng Sun,Bingxue Zhang,Minghao Peng

Asthma is characterized by airway inflammation and remodeling. 2-Undecanone (methyl nonyl ketone), a volatile organic compound originating from Houttuynia cordata, has the potential to ameliorate inflammatory diseases. This study aimed to explore potential benefits of 2-undecanone in asthma. 2-Undecanone (100, 200, or 400 mg/kg) was administered intragastrically to ovalbumin (OVA)-challenged BALB/c mice. Lung tissues were collected to observe histopathological changes, and bronchoalveolar lavage fluid (BALF) was collected for the detection of inflammatory cells and cytokine production. The results showed that 2-undecanone ameliorated OVA-induced pathologic changes of lungs, including reducing inflammatory cell infiltration, goblet cell hyperplasia, and airway smooth muscle thickness. The number of inflammatory cells and the levels of IL-4, IL-5, IL-13, and IgE in BALF were decreased by 2-undecanone in asthmatic mice. Furthermore, abnormal activation of NF-κB pathway in lung tissues of asthmatic mice was impeded by 2-undecanone. In vitro, 2-undecanone (12.5, 25, or 50 µM) suppressed platelet-derived growth factor-BB-induced proliferation and migration of primary airway smooth muscle cells (ASMCs), and inhibited the switching of ASMCs from contractile phenotype to synthetic phenotype. Consistently, 2-undecanone blocked NF-κB activation in ASMCs. Collectively, 2-undecanone relieves asthma through alleviating airway inflammation and remodeling, and this beneficial effect is achieved by inhibiting NF-κB pathway.

研究领域: 免疫学 · 药理学 · 呼吸医学
✓ 已验证 DOI PubMed 高影响因子
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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

Mild Hyperthermia-Assisted Coaxial Electrospun Nanofiber Patches for Epicutaneous Allergen-Specific Immunotherapy

Zhen Wang,Zhangyi Miao,Zhiting Cao,Jianye Ren,Xiaohong Zhu,Yu Sheng,Hao Cheng,Huaqing Zhang,Jianping Zhou,Yang Ding

Epicutaneous immunotherapy (EPIT) is effective and safe to induce sustained protection against anaphylaxis with small doses of allergens. To penetrate the barrier of the stratum corneum, a coaxial nanofiber patch is designed that incorporates natural phase-change materials (PCM) for mild hyperthermia-assisted skin permeability, while minimizing the risk of systemic events during immunotherapy. For adaptive immune activation, Toll-like receptor 7/8 ligand of resiquimod (R848) is combined with ovalbumin (OVA) allergen, thereby stimulating the Th1 pathway and strengthening therapeutic efficacy. For sequential administration, coaxial electrospinning technology is utilized for multiple drug encapsulation and sequential release, where the shell layer consists of poly(vinyl alcohol) (PVA) with OVA dispersion, and the core region is a mixture of PCM and R848. Under mild hyperthermia irritation, the nanofiber patches perform an efficient immunomodulation by manipulating the skin immune system via allergen/adjuvant combinations, which inhibits the secretion of OVA-specific IgE, and improves lung functions sufficiently in a mouse model of allergic asthma. Mechanistically, the treatment favors IgG2a expression from a Th1-biased immune response and induces protective regulatory immunity against allergen exposure. Overall, the simplicity and potency of mild hyperthermia mediated EPIT qualifies as a translational strategy for IgE-mediated allergies with long-lasting curative effects.

研究领域: 生物医学工程 · 免疫治疗 · 纳米技术 · 药学 · 过敏与免疫学
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FOOD CHEMISTRY · 2024 · IF 8.5

Modulating allergenicity of prawn tropomyosin (penaeus chinensis) via pulsed electric field-induced conformational changes

Xiangfei Hu,Hui Wang,Yueming Hu,Pingwei Wen,Xiongchen Wu,Zongcai Tu

The effect of electric field intensities (EFIs, 5–20 kV/cm) and treatment times (0.5–2 h) on allergenicity and spatial conformation of prawn tropomyosin was evaluated. The results demonstrated that the IgG and IgE binding capacity of tropomyosin maximally increased by 24.34 % and 29.16 % respectively, followed by a subsequent decrease after 20 kV/cm treatment for 1 h. Interestingly, 5–10 kV/cm treatments significantly decreased the α-helix content ( P  < 0.05) and fluorescence intensity, while 20 kV/cm treatment promoted extensive spiralization, resulting in a tightly packed structure. The increased flexibility further exposed the hydrolysis sites and strengthened the gastrointestinal digestibility of tropomyosin. Additionally, molecular dynamic simulation indicated that extended EFIs increased structural flexibility and depolymerized the tropomyosin dimers through destroying intermolecular hydrogen bonds (formed within arginine and glutamate), which allowed tropomyosin to be easily recognized by IgG/IgE. Whereas, decrease of solvent-accessibility surface area (SASA), hydrophobic surface area induced conformation folded and caused epitopes masked.

CAS / MDL: 69-78-3
研究领域: 食品科学 · 过敏研究 · 生物物理 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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