LARYNGOSCOPE
·
2022
·
IF 2.97
Tiancong Liu,Yang Sun,Zhaohui Guo,Weiliang Bai
Objectives Allergic rhinitis (AR) is an inflammatory autoimmune disease with disorder of the nasal mucosa. Cadherin 26 (CDH26), an alpha integrin-binding epithelial receptor, is regulated during allergic inflammation. This study aimed to investigate whether CDH26 contributes to the severity of AR. Study design In vivo and in vitro. Methods We investigated the effects of CDH26 knockdown by lentivirus (LV)-mediated shRNA on ovalbumin (OVA)-induced AR mice and IL-13-stimulated human nasal epithelial cells (NECs). Results CDH26 mRNA and protein expression was significantly increased in the nasal mucosa of AR patients and mice. Intranasal instillation of LV-shCDH26 alleviated allergic symptoms and decreased the histological changes of nasal mucosa in AR mice. Furthermore, the serum levels of OVA-specific IgE, IgG, pro-inflammatory factors IL-25, IL-33, and TSLP were decreased in AR mice with CDH26 knockdown. With regard to AR-induced Th2 inflammation, LV-shCDH26 intervention effectively decreased the distribution of CD4 + /GATA3 + Th2 cells, and the mRNA expression of IL-4, IL-5, and IL-13 in the nasal mucosa. CDH26 knockdown down-regulated the expression of β-catenin but not for E-cadherin and ZO-1 in nasal mucosa induced by AR. In vitro, CDH26 knockdown inhibited the protein expression of TSLP, GM-CSF and eotaxin in NECs, and CDH26 overexpression remarkably promoted the production of these inflammatory factors in IL-13-induced NECs. Conclusions CDH26 knockdown attenuates the AR-induced inflammatory response both in vivo and in vitro. Level of Evidence NA Laryngoscope , 2022
研究领域:
免疫学
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分子生物学
·
过敏
·
呼吸医学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Hui-Hui Guo,Yan-Xing Han,Xiao-Juan Rong,Zhen Shen,Hao-Ran Shen,Ling-Fei Kong,Yun-Dan Guo,Ji-Zhou Li,Bo Xu,Tian-Le Gao,Lu-Lu Wang,Cai Tie,Jian-Dong Jiang
Background Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. Purpose To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. Methods We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. Results RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress. Conclusions The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.
研究领域:
药理学
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免疫学
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微生物学
·
呼吸医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Feifan Liu,Yuanmei Bai,Xue Wu,Yan Wan,Shifang Luo,Linao Zhang,Tao Li,Hua Tang,Xianjin Tang,Rong Chen,Qinghua Chen,Yuhuan Xie,Peixin Guo
Ethnopharmacological relevance Allergic rhinitis (AR) stands as a non-infectious inflammatory condition affecting the nasal mucosa, marked by bouts of sneezing, nasal itching, and congestion. This ailment afflicts individuals across all age groups and poses challenges for effective treatment due to its chronic nature. Cangerzisan (CEZS), documented in the Jishengfang compendium, represents a traditional Chinese medicinal formula long utilized for AR management. Aim of the study : Investigating mechanism beneath therapeutic effect of CEZS in alleviating AR. Materials and methods The main active components in CEZS were determined by High Performance Liquid Chromatography (HPLC).The active constituents of CEZS and their corresponding targets were identified through an exhaustive screening process employing TCMSP database. To identify targets relevant to AR, GeneCards, OMIM, and DisGeNET databases were thoroughly applied. Protein-protein interaction (PPI) network was assembled utilizing STRING platform. Potential signaling pathways influenced by CEZS were delineated through GO and KEGG enrichment analyses. Subsequently, an AR model was induced by administering aluminum hydroxide (Al(OH)3) and ovalbumin (OVA) for affecting basal and local sensitization, respectively, facilitating experimental validation of the principal signaling pathways. Results There were 61 active constituents identified within CEZS, targeting a pool of 129 entities associated with AR treatment. Pathways analysis of KEGG revealed that CEZS potentially inhibits AR advancement via modulating TLR4 signaling pathway. Animal experiments demonstrated that CEZS effectively alleviated symptom scores in guinea pigs with AR. Moreover, it exhibited notable improvements in serum immune and inflammatory factors levels, as well as reduced inflammatory infiltration within nasal mucosa, including goblet and mast cells. CEZS was found to enhance GATA-3 expression while reducing T-bet expression, thereby modulating the TH1/TH2 immune balance. Additionally, CEZS downregulated HMGB1, TLR4, and p–NF–κB/NF-κB protein expressions within nasal mucosa of guinea pigs. Conclusions The therapeutic mechanism of CEZS against AR involves rectifying TH1/TH2 immune imbalance and upregulating inflammatory and immune factors through modulating key proteins expression within TLR4 pathway. This targeted regulation effectively impedes AR progression.
研究领域:
民族药理学
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药理学
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免疫学
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传统中药
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生物信息学
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实验验证
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2024
·
IF 5.6
Yanan Liu,Huan Li,Chong Wang,Shanjun Chen,Renjie Lian,Weiqiang Wang,Linglin Fu,Yanbo Wang
Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk. However, its influences on immunological components, especially the function of key immune cells, are still poorly known. In this work, we explored the effects of exogenous histamine on the function of key immune cells such as intestinal epithelial cells, dendritic cells, and T cells. The results showed that histamine could affect the expression of allergy-related genes in CMT93 cells at a high dose of histamine. Moreover, it’s found that histamine could cause an imbalance in the levels of relevant immune factors secreted by dendritic cells and T cells, especially those related to allergy. At the same time, the proportion of MHC class II-positive dendritic cells and the proportion of T helper 2 (Th2) cells in CD4 + T cells increased after histamine stimulation. We concluded that the presence of a certain level of histamine in food may affect the expression of allergy-related cytokines, disrupt the balance of the immune homeostasis, and potentially lead to adverse immune reactions. This work demonstrated the importance of including the estimation of histamine's immune safety in aquatic products rather than merely considering the potential risk of food poisoning.
研究领域:
免疫学
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食品科学
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毒理学
✓ 已验证
产品关联
DOI
高影响因子
Food Bioscience
·
2025
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IF 5.9
Cuifang Wang,Zihan Zhang,Linhui Xie,Sili Ji,Chao Zhao,Congjie Dai
s Food allergy (FA) has emerged as a pivotal concern for food safety and public health worldwide. Among marine-derived nutrients, fucoidans have shown promising anti FA potential, yet the absence of studies on well-defined fucoidan structures has made it quite challenging to establish a clear relationship between their structure and anti-allergic activity. Our previous studies demonstrated that crude fucoidan from Sargassum graminifolium substantially ameliorated FA symptoms and further isolation yielded a S. graminifolium fucoidan SGF-2. Nevertheless, its structural characteristics and anti FA properties remain elusive. In this study, we elucidated the major backbone linkages of SGF-2 via methylation analysis combined with nuclear magnetic resonance (NMR) spectroscopy and evaluated its anti FA potential in an ovalbumin (OVA)-sensitized mouse model. The results showed that SGF-2 intervention effectively mitigated FA symptoms by markedly reducing OVA-specific Immunoglobulin E (IgE) and related cytokines levels, decreasing the incidence of diarrhea and the spleen index, and suppressing intestinal inflammation. 16S_rRNA sequencing analysis demonstrated that SGF-2 interventions could effectively counteract gut microbiota disruption induced by FA by partially enhancing microbial community diversity, augmenting the relative abundances of probiotics that produce short-chain fatty acids (SCFAs), and suppressing the relative abundances of harmful bacteria. Furthermore, the levels of SCFAs in feces increased following interventions with SGF-2. Flow cytometry analysis revealed that SGF-2 reversed the imbalance of Th1/Th2 polarization, particularly by inhibiting the Th2-type immune response and promoting the differentiation of Regulatory T cells (Tregs). These findings suggest that fucoidan derived from S. graminifolium holds great promise for the development of functional foods.
研究领域:
食品科学
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免疫学
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海洋生物技术
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结构生物学
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微生物学
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生物化学
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营养科学
✓ 已验证
产品关联
DOI
高影响因子
Materials Horizons
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2024
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IF 12.2
Wenzhu Yin,Zeyu Xu,Chen Chang,Yanhong Zhao,Haiyan Wang,Jinqiu Zhang,Fang Ma,Xiaoxin Zuo,Bo Tang,Yu Lu
Pseudorabies virus (PRV) is a highly contagious viral disease, and leads to severe financial losses to the breeding industry worldwide. The PRV is mainly controlled using live attenuated and inactivated vaccines today. However, these vaccines have an innate tendency to lose their structural conformation upon environmental and chemical stressors, and can’t provide full protection against the prevalent variant PRV recently. In this work, we firstly synthesized aminated ZIF-7/8 nanoparticles (NPs), and then chemical bond coated alginate dialdehyde (ADA, a kind of dioxide alginate saccharides) on its surface via Schiff base reaction to get ZIF-7/8-ADA NPs. The as-fabricated ZIF-7/8-ADA NPs exhibited high stability, monodispersity and a high loading ratio of antigen. Furthermore, ZIF-7/8-ADA NPs showed good biocompatibility in vitro and in vivo. Using ZIF-7/8-ADA NPs as an adjuvant and inactivated PRV as the model antigen, we constructed a PR vaccine through a simple mixture. Immunity studies indicated that ZIF-7/8-ADA induced an enhancing Th1/Th2 immune response, which was superior to that of commercial ISA201, Alum adjuvant as well as ZIF-7/8. Due to the pH-sensitive release of the antigen in lysosomes, the as prepared PR vaccine subsequently accelerated antigen presentation and improved immune responses in vitro and in vivo. The results of challenge against PRV using mice as model proclaimed that ZIF-7/8-ADA could obtain the same preventive effect as commercial ISA201, and was much better than that of alum adjuvant, which could serve as a promising delivery and adjuvant to enhance humoral and cellular responses against PRV infection.
研究领域:
病毒学
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免疫学
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纳米技术
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
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IF 13
Yapeng Wang,Jing Yang,Yunhong Ma,Jun Liu,Peng Wang,Junhao Luo,Yongjun Rui,Yongwei Wu
The accumulation of excessive reactive oxygen species (ROS) and recurrent infections with drug-resistant bacteria pose significant challenges in diabetic wound infections, often leading to impediments in wound healing. Addressing this, there is a critical demand for novel strategies dedicated to treating and preventing diabetic wounds infected with drug-resistant bacteria. Herein, 2D tantalum carbide nanosheets (Ta 4 C 3 NSs) have been synthesized through an efficient and straightforward approach, leading to the development of a new, effective nanoplatform endowed with notable photothermal properties, biosafety, and diverse ROS scavenging capabilities, alongside immunogenic attributes for diabetic wound treatment and prevention of recurrent drug-resistant bacterial infections. The Ta 4 C 3 NSs exhibit remarkable photothermal performance, effectively eliminating methicillin-resistant Staphylococcus aureus ( MRSA ) and excessive ROS, thus promoting diabetic wound healing. Furthermore, Ta 4 C 3 NSs enhance dendritic cell activation, further triggering T helper 1 (T H 1)/T H 2 immune responses, leading to pathogen-specific immune memory against recurrent MRSA infections. This nanoplatform, with its significant photothermal and immunomodulatory effects, holds vast potential in the treatment and prevention of drug-resistant bacterial infections in diabetic wounds.
研究领域:
纳米技术
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生物医学工程
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传染病学
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免疫学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-33
·
IF 10.6
Liu Jianyu,Wang Meiqun,Tian Xiaoyan,Wu Shuhong,Peng Haisen,Zhu Yaqiong,Liu Yuehui
Allergic rhinitis (AR) is a condition with limited treatment options. This study investigates the potential use of mesenchymal stem cell (MSC) nanovesicles as a novel therapy for AR. Specifically, the study explores the underlying mechanisms of MSC nanovesicle therapy by targeting dendritic cells (DCs). The researchers fabricated DC-targeted P-D2-EVs nanovesicles and characterized their properties. Transcriptomic sequencing and single-cell sequencing analyses were performed to study the impact of P-D2-EVs on AR mice, identifying core genes involved in the treatment. In vitro cell experiments were conducted to validate the effects of P-D2-EVs on DC metabolism, Th2 differentiation, and ILC2 activation. The results showed that P-D2-EVs efficiently targeted DCs. Transcriptomic sequencing analysis revealed differential expression of 948 genes in nasal tissue DCs of mice treated with P-D2-EVs. Single-cell sequencing further revealed that P-D2-EVs had inhibitory effects on DC activation, Th2 differentiation, and ILC2 activation, with Fut1 identified as the core gene. Validation experiments demonstrated that P-D2-EVs improved IL10 metabolism in DCs by downregulating Fut1 expression, thereby suppressing Th2 differentiation and ILC2 activation. Animal experiments confirmed the inhibitory effects of P-D2-EVs and their ability to ameliorate AR symptoms in mice. The study suggests that P-D2-EVs reshape DC metabolism and suppress Th2 differentiation and ILC2 activation through the inhibition of the Fut1/ICAM1/P38 MAPK signaling pathway, providing a potential therapeutic approach for AR. Graphical Abstract
研究领域:
免疫学
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分子生物学
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细胞生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL ALLERGY
·
2021
·Vol. 52
·期 1
·46-58
·
IF 5.018
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.
研究领域:
免疫学
·
肺科学
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过敏学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Jiuyan Zhang,Yuan Zhao,Ning Sun,Manyu Song,Yongping Chen,Lin Li,Hailin Cui,Haotian Yang,Chuqiao Wang,Haiyang Zhang,Honggang Fan
Chronic stress induction in immunosuppression and splenocyte apoptosis is commonly associated with increased susceptibility to various diseases. Lycopene (LYC) is a member of the carotenoid family with immune restoration and anti-apoptotic function. However, little is known about the mechanisms underlying the protective roles of LYC against spleen injury induced by chronic stress. Herein, male Wistar rats were undergoing chronic restraint stress and/or administered LYC (10 mg/kg) for 21 days. The effective model establishment was validated by open-field tests and levels of corticosterone in serum. Histopathological staining observation displayed that LYC could reduce chronic stress-induced spleen structure damage. Furthermore, LYC treatment significantly reduced the number of apoptotic-positive splenocytes caused by chronic stress via the death receptor apoptotic pathway. We detected the interleukin 4 and interferon γ levels in serum and spleen to determine the ratio of Th1 and Th2 and found that LYC can alleviate the immunosuppression induced by chronic stress. Notably, western blot and real-time polymerase chain reaction indicated that LYC can reduce the expression of the Notch-pathway-related proteins and mRNA in rats exposed to chronic stress. Further study of the potential mechanisms by adding the Notch pathway inhibitor DAPT revealed that LYC alleviates the structure damage, apoptosis, and immunosuppression caused by chronic stress via the suppression of the Notch pathway. Overall, this study presents a strong rationale to target LYC as a treatment strategy to relieve chronic stress-induced spleen injury.
研究领域:
免疫学
·
药理学
·
分子生物学
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应激生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
·
IF 10
Wei Liu,Di Liu,Tianyi Cui,Yili Wang,Sufei Zhou,Fangzhen Tian,Ke Yang,Wei Wang,Lewei Bi,Kelong Fan,Lan Li,Hao Wang,Xiao-Dong Zhang
Pneumonia involves complex immunological and pathological processes leading to pulmonary dysfunction, which can be life-threatening yet lacks effective specialized medications. Natural enzymes can be used as biological agents for the treatment of oxidative stress-related diseases, but limiting to catalytic and environmental stability as well as high cost. Herein, an artificial enzyme, gold nanoclusters (Au NCs) with excellent stability, bioactivity, and renal clearance can be used as the next-generation biological agents for acute lung injury (ALI) and allergic lung disease (ALD). The Au 25 clusters can mimic catalase (CAT) and glutathione peroxidase (GPx), and the K m of Au 24 Er 1 with H 2 O 2 reaches 1.28 mM, about 22 times higher than natural CAT (≈28.8 mM). The clusters inhibit the oxidative stress in the mitochondria and promote the synthesis of adenosine triphosphate (ATP). The molecular mechanism shows that the TLR4/MyD88/NF-κB pathway and M1 macrophage-mediated inflammatory response are suppressed in ALI and the Th1/Th2 imbalance in ovalbumin (OVA)-induced ALD is rescued. Further, the clusters can notably improve lung function in both ALI and ALD models which paves the way for immunomodulation and intervention for lung injury and can be used as a substitute for natural enzymes and potential biopharmaceuticals in the treatment of various types of pneumonia.
研究领域:
纳米技术
·
免疫学
·
药理学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2024
·
IF 5.7
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.
研究领域:
免疫学
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过敏
·
微生物学
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分子生物学
✓ 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）