BIOMEDICINE & PHARMACOTHERAPY
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2022
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IF 7.419
Cheng Wang,Yajing Hou,Shuai Ge,Jiayu Lu,Xiangjun Wang,Yuexin Lv,Nan Wang,Huaizhen He
Anaphylaxis is a severe systemic allergic reaction that exhibits multiple clinical symptoms. The Mas-related G protein-coupled receptor X2 (MRGPRX2) is recognized as a key cell receptor mediating allergic diseases and drug-induced anaphylactoid reactions. Thus, it has been a promising target for preventing and treating these reactions. Based on the potential activity of imperatorin and active structural feature of MRGPRX2, we first demonstrated that the synthetic imperatorin derivatives (IDs) could significantly inhibit MRGPRX2 agonist-induced degranulation and cytokine release in LAD2 cells, as well as alleviate local and systemic anaphylaxis in mice. The IC 50 value of the most promising compound is an order of magnitude lower than that of imperatorin. IDs were further identified to display anti-pseudo-allergic activity by binding MRGPRX2 with the tertiary nitrogen substructures, just liking the reported MRGPRX2-ligand. These results would propose evidence for discovery of agents for treating MCs-dependent allergic disorders.
研究领域:
免疫学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MICRON
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2019
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IF 1.53
Jing Hu,Yujuan Chen,Jiajing Zhu,Mingyan Gao,Jiani Li,Zhengxun Song,Hongmei Xu,Zuobin Wang
Allergic diseases not only bring serious economic burden to the patients, but also consume a lot of substantial resources of social medical systems. Thus, the prevention and treatment of allergic diseases are imperative. In this study, the anti-degranulation activity of herbal formula was evaluated using the rat basophil leukemia cells (RBL-2H3) as in vitro model. The morphological and biophysical properties of RBL-2H3 cells before and after treatment with herbal formula were also determined. Notably, the herbal formula exhibits clearly inhibited degranulation by RBL-2H3 cells in a concentration-dependent manner without cytotoxic effect. Therefore, this herbal formula can be used as an alternative and promising therapeutic agent to ameliorate allergic diseases.
研究领域:
药理学
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免疫学
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过敏研究
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2023
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IF 4.3
Meitong Liu,Jing Lu,Qingbin Liu,Yuelin Chen,Guang Wang,Qian Zhang,Shuang Guan
Sodium metabisulphite (SMB) is the most used foods and drugs antioxidant among sulfites . So far, there were few studies about its harm, especially in mast cells. Our study was to investigate the effects of SMB on mitophagy and pyroptosis in mast cells. The results revealed that SMB dose-dependently promoted the expressions of NLRP3, GSDMD-N and other marker proteins of pyroptosis. Knockdown of GSDMD, NLRP3 inhibitor, mitophagy activator and mtROS inhibitor all reversed the changes in pyroptosis indicators caused by SMB. Considering the degranulation characteristics of mast cells and the sensitization of sulfite, we examined the effects of the above inhibitors on the degranulation of mast cells caused by SMB. The results showed that SMB-mediated mast cell degranulation was significantly inhibited by the above inhibitors. Meanwhile, we used immunofluorescence co-localization experiments and found that GSDMD pore-forming protein and histamine co-localized near the cell membrane. Overall, evidence suggested that SMB caused pyroptosis by inhibiting mitophagy, leading to mast cell degranulation. These findings are of great significance to the sensitization mechanism of SMB and provide a new insight into SMB toxicology and mast cell degranulation.
研究领域:
毒理学
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免疫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CRYOBIOLOGY
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2018
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IF 2.05
Hao Xu,Wenyue Cao,Liang Huang,Min Xiao,Yang Cao,Lei Zhao,Na Wang,Jianfeng Zhou
Chimeric antigen receptor T (CART) cell therapy has emerged as a potentially curative “drug” for cancer treatment. Cryopreservation of CART cells is necessary for their clinical application. Systematic studies on the effects of cryopreservation on the antitumor function of CART cells are lacking. Therefore, we compared the phenotypes and functions of CART cells that were cryopreserved during ex vivo expansion with those of freshly isolated populations. T cells expressing an anti-B-cell-maturation-antigen (BCMA) chimeric antigen receptor (CAR) were expanded in vitro for 10 days and then cryopreserved. After one month, the cells were resuscitated, and their transduction rates, apoptosis rates and cell subsets were examined via flow cytometry. The results indicated no significant changes in transduction rates or cell subsets, and the survival rate of the resuscitated cells was approximately 90% Furthermore, similar tumoricidal effects and degranulation functions of the resuscitated cells compared with normally cultured cells were verified by calcein release and CD107a assays. A NOD/SCID mouse model was used to estimate the differences in the in vivo antitumor effects of the cryopreserved and normally cultured T cells, but no significant differences were observed. Following co-culture with several target cell types, the cytokines released by the cryopreserved and normally cultured T cells were measured via enzyme-linked immunosorbent assays (ELISAs). The results revealed that the release of interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) was significantly decreased. These data demonstrated that with the exception of a decrease in cytokine release , the cryopreserved CART cells retained their antitumor functions.
研究领域:
肿瘤学
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免疫治疗
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Food Science and Human Wellness
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2023
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IF 7
Jie Ding,Chunyan Zhu,Pengfei Jiang,Libo Qi,Na Sun,Songyi Lin
Enzymatic hydrolysis, isolation, and purification might make a great deal of difference in antioxidant activity and antigenicity of peptide components. This study aimed to isolate and purify antioxidant peptide components from Antarctic krill and evaluate their allergenicity of them. Electron paramagnetic resonance (EPR) spectroscopy results indicated 3 10 kDa Antarctic krill hydrolysates (AKHs) had higher DPPH and · OH radical scavenging rates. And the second component (N2-2) purified 3 10 kDa hydrolysate showed better ability to scavenge DPPH and · OH radicals ( P < 0.05), which were (47.43 ± 2.18)% and (34.33 ± 1.25)%, respectively. Additionally, indirect-ELISA results revealed that N2-1 had a weaker ability to bind specific IgE and that N2-2 had a lower binding capability to specific IgG1 ( P < 0.05). And N2-2 had a higher EC 50 value of (5.29 ± 0.95) ng/mL ( P < 0.05) in cell degranulation assay, which was about 13.80 times that of Antarctic krill. Therefore, N2-2 might be the potential source of the antioxidant peptides with lower allergenicity.
研究领域:
食品科学
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生物化学
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
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2023
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IF 4.1
Xiaoqian Xu,Qiang Cao,Jin Yuan,Ping Tong,Xin Li,Anshu Yang,Zhihua Wu,Xiaohua Liu,Hongbing Chen,Jinyan Gao
BACKGROUND The interaction between food allergens and plant polyphenols has become a safe and effective management strategy to prevent food allergies. Ovalbumin (OVA) is the most abundant allergen in egg whites. Resveratrol (RES) is a plant polyphenol that is abundant in red grapes, berries, and peanuts, and has an anti-allergic effect on allergy-related immune cells. However, there is little information about the effect of RES on the allergenicity of OVA. In this study, the effect of RES on the allergenicity of OVA was investigated. RESULTS Molecular docking and spectroscopic studies indicated that the addition of RES changed the structure of OVA. The digestion and transfer rate of OVA–RES were effectively improved with an in vitro gastrointestinal digestion model and Caco-2 cell model, especially when the molar ratio of OVA–RES was 1:20. Meanwhile, the KU812 cell degranulation assay proved that the potential allergenicity was remarkably decreased while the molar ratios of OVA–RES were increased to 1:20. Furthermore, hydrogen bonds and van der Waals forces were the dominating forces to stabilize the OVA–RES complexes. CONCLUSION All the findings demonstrated that the potential allergenicity of OVA was reduced when interacting with RES, and RES can be a potential food material for preparing a hypoallergenic protein, especially for egg allergy. © 2023 Society of Chemical Industry.
研究领域:
食品科学
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过敏研究
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分子生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
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2022
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IF 4.271
Yan Zhou,Mengmeng Wei,Mingkang Zhang,Jianping Zhang,Fabing Tang,Xin’an Wu
Organic anion transporters 1 (OAT1) and OAT3 are responsible for transporting adefovir (ADV) into renal tubular epithelial cells. Our previous research found that ADV accumulated in the renal interstitium and caused renal interstitial fibrosis when Oat1/3 were inhibited by OATs inhibitor probenecid for long-term. Mast cells (MCs) in the interstitial space are considered to be key drivers of renal fibrosis. The current work investigated the effect of ADV on MCs in vitro and during the development of interstitial fibrosis in rats. Results indicate that ADV triggers chymase release from cultured RBL-2H3 mast cells in a time-and concentration-dependent manner. Angiotensin II (Ang II) in renal interstitium is generated mainly by chymase, renin and other products released from MCs, and has a direct effect on fibrosis through the angiotensin receptor. The concentrations of Ang II and fibrosis was significantly increased after administration of ADV alone or with probenecid for 4 weeks. The MCs membrane stabilizer sodium cromoglycate (SCG) and the angiotensin receptor antagonist Valsartan (VAL) could ameliorate ADV-induced nephrotoxicity. Additionally, SCG or VAL could reduce the accumulation of ADV in the renal interstitium by upregulating the expression of Oat1/3 and multidrug resistance-associated protein 4. Therefore, ADV accumulation in the renal interstitium could promote the degranulation of interstitial MCs and drive the development of renal fibrosis. SCG or VAL could ameliorate ADV-associated fibrosis by decreasing degranulation of MCs and accelerating renal clearance of ADV.
研究领域:
药理学
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肾病学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2025
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IF 7.3
Ziyuan Li,Pu Chen,Yongfeng Lin,Jingxu Zhang,Jian Ding,Rifat Zubair Ahmed,Xiaoting Jin,Yuxin Zheng
Tris (2-chloroethyl) phosphate (TCEP), recognized as an emerging pollutant, has been frequently detected in human blood. Maintenance of blood homeostasis is indispensable for regulating various physiological states and overall health, yet hematological toxicology of TCEP has not been extensively investigated. Platelets, a vital component of blood, are fundamental in the processes of hemostasis and thrombosis through their activation; thus, this study was designed to elucidate the effects and underlying mechanisms of TCEP on platelet activation. Utilizing an in vivo model, we conducted a proteomic analysis of platelets and found that TCEP exposure inhibited platelet activation. An ex vivo platelet evaluation system was employed to further dissect the processes of platelet activation, revealing that TCEP predominantly suppressed platelet aggregation, degranulation and clot retraction. These processes were highly dependent on energy metabolism, and TCEP was found to decrease ATP levels, primarily by impairing glycolysis and pentose phosphate pathways. Subsequent investigation into the molecular mechanisms revealed that TCEP decreased the activity of phosphofructokinase platelet (PFKP) by enhancing O-linked N-acetylglucosamine (O-GlcNAc) transferase interaction with PFKP. This study is the first to uncover the disruptive effects of TCEP on platelet activation process, providing valuable insights into the assessment of hematologic health risks associated with TCEP-like emerging pollutants exposure.
研究领域:
血液学
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毒理学
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分子生物学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2023
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IF 8.1
Songsong Jiang,Tao Wang,Kuan Chen,Hengpeng Wang,Xiangren Meng
Sesame allergy is a growing concern worldwide. In this study, sesame proteins was glycated with glucose, galactose, lactose and sucrose respectively, and the allergenicity of different glycated sesame proteins were assessed by a comprehensive strategy, including simulated gastrointestinal digestion in vitro , a BALB/c mice model, a rat basophilic leukemia (RBL)–2H3 cell degranulation model and a serological experiment. Firstly, simulated gastrointestinal digestion in vitro showed that glycated sesame proteins were more easily to digest than raw sesame. Subsequently, the allergenicity of sesame proteins was assessed in vivo by detecting the allergic indexes of mice, and results showed that the levels of total immunoglobulin E (IgE) and histamine were reduced in glycated sesame proteins treated mice. Meanwhile, the Th2 cytokines (IL-4, IL-5, and IL-13) were downregulated significantly, demonstrating that sesame allergy was relieved in glycated sesame treated mice. Thirdly, the RBL-2H3 cell degranulation model results showed that the release of β-hexosaminidase and histamine were decreased to different degrees in glycated sesame proteins treated groups. Notably, the monosaccharide glycated sesame proteins exhibited lower allergenicity both in vivo and in vitro . Furthermore, the study also analyzed the structure alteration of sesame proteins, and the results showed that the secondary structure of glycated sesame proteins were changed (the content of α-helix and β-sheet were reduced), and the tertiary structure of sesame proteins after glycation modification was also changed (microenvironment around aromatic amino acids was altered). Besides, the surface hydrophobicity of glycated sesame proteins was also reduced except sucrose glycated sesame proteins. In conclusion, this study demonstrated that glycation reduced the allergenicity of sesame proteins effectively, especially glycation with monosaccharides, and the allergenicity reduction might be related to structural changes. The results will provide a new reference for developing hypoallergenic sesame products.
研究领域:
食品科学
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过敏研究
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蛋白质化学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）