IMMUNITY
·
2021
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IF 31.745
Ling-jie Huang,Xin-tao Mao,Yi-yuan Li,Dan-dan Liu,Ke-qi Fan,Rong-bei Liu,Ting-ting Wu,Hao-li Wang,Yu Zhang,Bing Yang,Cun-qi Ye,Jiang-yan Zhong,Ren-jie Chai,Qian Cao,Jin Jin
Summary Inflammatory bowel disease (IBD) mainly includes Crohn’s disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.
研究领域:
免疫学
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胃肠病学
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代谢组学
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系统生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Donghui Li,Wenbo Li,Sheng Li,Yangyang Zhang,Xianwen Hu,Shilin Liu,Yan Li
Nasal vaccine is a non-invasive vaccine that activates systemic and mucosal immunity in the presence of an adjuvant, thereby enhancing immune function. In this work, chitosan/oligochitosan/tween 80 (CS-COS-T80) co-stabilized emulsion was designed and further used as the nasal adjuvant. CS-COS-T80 emulsion exhibited outstanding stability under pH 6–8 with uniformly dispersed droplets and nano-scale particle size (<0.25 μm), and maintained stable at 4 °C for 150-day storage. Addition of model antigen ovalbumin (OVA) had no effect on the stability of CS-COS-T80 emulsion. In vivo nasal immunity indicated that CS-COS-T80 emulsion prolonged the retention time of OVA in the nasal cavity (from 4 to 8 h to >12 h), as compared to T80-emulsion. CS-COS-T80 emulsion produced a stronger mucosal immune response to OVA, with secretory IgA levels 5-fold and 2-fold higher than those of bare OVA and commercial adjuvant MF59, respectively. Compared to MF59, CS-COS-T80 induced a stronger humoral immune response and a mixed Th1/Th2 immune response of OVA after immunization. Furthermore, in the presence of CS-COS-T80 emulsion, the secretion of IL-4 and IFN-γ and the activation of splenocyte memory T-cell differentiation increased from 173.98 to 210.21 pg/mL and from 75.46 to 104.01 pg/mL, respectively. Therefore, CS-COS-T80 emulsion may serve as a promising adjuvant platform.
研究领域:
药学
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免疫学
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生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Infectious Diseases
·
2023
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IF 5.3
Wenzhu Yin,Bihua Deng,Zeyu Xu,Haiyan Wang,Fang Ma,Mingxu Zhou,Yu Lu,Jinqiu Zhang
Adjuvants are essential for the induction of robust immune responses against vaccine antigens. Small-molecule TLR7 agonists hold high potential for this purpose. In this communication, imiquimod (IMQ) bearing a cholesterol lipid moiety derivative, IMQ-Chol, was designed and synthesized as a vaccine adjuvant, which could release parent IMQ molecules in aqueous conditions via amide bond hydrolysis. We performed a series of immunological evaluations by cooperating with the inactivated foot-and-mouth disease virus (FMDV). All of the results confirmed that IMQ-Chol could stimulate the body for a prolonged time to produce strong humoral and cellular immunity with a balanced Th1/Th2 immune response through a TLR7-related MAPK pathway. In addition, the results of the proof-of-concept vaccine indicated IMQ-Chol had a good effect on preventing and treating FMD in pigs.
研究领域:
免疫学
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病毒学
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药学
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兽医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2023
·
IF 5.2
Xiaoying Tian,Xi Liang,Hong He,Qingyu Cui,Qiqi Liu,Rongbo Fan,Tongjie Liu,Huaxi Yi,Pimin Gong,Qingzhu Wang,Lanwei Zhang
Scope Food allergy has become a world recognized public health problem due to its versatility and lack of efficacious methods for its treatment. Probiotics supplement is a potential way to prevent food allergy. Methods and results In this study, potential strains are screen out by peripheral blood mononuclear cells (PBMCs), and their abilities of alleviating food allergy are examined using a mouse model induced by ovalbumin (OVA). The results show that six strains increase ratio of interferon-γ (IFN-γ)/interleukin (IL)-4 secreted by PBMCs with good abilities in intestinal adhesion and gastrointestinal tolerance. Oral administration of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) attenuates allergic responses in allergy mice, including allergic symptoms, mast cells aggregation and activity, serum OVA-special-immunoglobulins E (OVA-sIgE) production. KV9 and FN3 upregulate the production of IFN-γ/IL-4 in splenocytes, increase the genes and proteins expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (Myd88) and interferon regulatory factor (IRF)-1 in allergic mice spleen, and decrease the IRF-4. Conclusion The study demonstrates that KV9 and FN3 possess anti-allergic activities via activation of TLR4 pathway and modulating the expression of IRF-1 and IRF-4 which leads to T helper type 1 (Th1)/T helper type 2 (Th2) cell immunology balance.
研究领域:
免疫学
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微生物学
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过敏
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
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IF 3.943
Meng Wang,Jinglan Zhang,Huayan Zhao,Dingming Wan,Zhongxing Jiang
Graft-versus-host disease (GVHD) causes significant mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Berberine (BBR) is primarily used to alleviate inflammation caused by autoimmune disorders. Herein the effect of BBR and cyclosporine A (CsA) on GVHD prevention in murine models is explored. Acute GVHD was induced by total body irradiation and tail vein injection with the mixture of bone marrow cells and spleen lymphocytes. Then models were treated with BBR (10 mg/kg), CsA (5 mg/kg) or the combination of BBR and CsA (10 mg/kg and 5 mg/kg) once a day for 10 days. The survival rate, weight loss and GVHD index were monitored. Then the histological changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, apoptosis and the levels of inflammatory cytokines, oxidative stress and nuclear factor-κB (NF-κB) signaling in liver and intestine were analyzed. Moreover, the levels of inflammatory cytokines and oxidative stress, and the count of T helper 1 (Th1) cells and Th17 cells in peripheral blood were determined. The results showed that BBR reduced GVHD-induced weight loss and GVHD index scores, attenuated liver and intestinal injury, and inhibited ALT and AST activities, inflammation, oxidative stress and NF-κB activation in liver and intestine. Additionally, BBR inhibited inflammation and reduced Th1 cell counts but had no effect on Th17 cell counts. Interestingly, the concomitant therapy of BBR and CsA was more potent than either BBR or CsA and effectively elevated the survival rate of GVHD models. This present study provides a new therapeutic strategy for alleviation of acute GVHD.
研究领域:
免疫学
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药理学
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血液学
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移植学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
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IF 13.2
Xudong Xie,Weixian Hu,Yue An,Yuheng Liao,Shengming Zhang,Yanzhi Zhao,Kangkang Zha,Wenqian Zhang,Zhenhe Zhang,Fan Xia,Bobin Mi,Benjie Zhou,Hankun Hu,Mengfei Liu,Guohui Liu
Diabetic wounds are characterized by an imbalance between impaired angiogenesis and persistent pro-inflammatory immune responses, leading to chronic non-healing. Under hyperglycemic and oxidative stress conditions, the glycolytic function of endothelial cells is significantly compromised. However, solely enhancing angiogenesis does not effectively promote diabetic wound healing due to concomitant dysregulation of the local immune microenvironment, which further suppresses vascularization. Notably, Th1 cells dominate the diabetic wound immune milieu and exacerbate inflammatory responses, thereby aggravating immune imbalance. Thus, an optimal therapeutic strategy should simultaneously target both inflammatory dysregulation and vascular dysfunction. To address the phenomenon of cell-specific metabolic reprogramming within diabetic wounds, where glycolytic activity is impaired in endothelial cells yet enhanced in Th1 cells, this study developed a glucose-responsive NG@B87@HA hydrogel system designed to reprogram the local metabolic network and modulate Th1 cell metabolism while restoring endothelial function. The hydrogel incorporates nanoparticles functionalized with CXCR3 antibody to specifically target Th1 cells and deliver the glycolysis inhibitor Bay87-2243 (B87), thereby suppressing their glycolytic flux and inflammatory activity via inhibition of the HIF-1α–GLUT1 signaling axis. Simultaneously, naringin (NG), which acts as a crosslinker, forms dynamic boronic ester bonds with HA-PBA and PVA, enabling glucose-dependent responsiveness. This mechanism not only mitigates local oxidative stress but also enhances the tube-forming capacity of endothelial cells, ultimately promoting angiogenesis. The results demonstrated that the NG@B87@HA hydrogel effectively restores the dysregulated metabolic network in diabetic wounds. By concurrently rectifying immune microenvironment imbalance and endothelial dysfunction, this system provides a novel therapeutic strategy for accelerating diabetic wound healing.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2018
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IF 3.115
Wenhao Xu,Meiqun Hu,Qihong Zhang,Jingbo Yu,Weike Su
Ethnopharmacological relevance Cassia occidentalis Linn. is a traditional ayruvedic edible shrub containing anthraquinones (AQs) as the principle active constituents. In folk medicine, it has a variety of uses including treatment of whooping cough (‘pertussis’) and inflammatory diseases . Despite these applications, limited data are available to validate the effects of C. occidentalis AQs on airways inflammation in asthma. Aim of the study To explore the anti-inflammatory potential of AQs extracted from C. occidentalis using an in vivo model of ovalbumin (OVA)-induced asthma. Materials and methods Extraction and optimization of AQs from C. occidentalis was performed by mechanochemistry. Allergic asthma in BALB/c mice was sensitized and challenged by OVA, and the effects of AQs investigated in a mouse model. OVA-specific IgE concentrations in serum, and Th1/Th2 cytokine (IL-4, IL-5, IL-13 and IFN- γ ) concentrations, inflammatory cell counts and classification in bronchoalveolar lavage fluid (BALF) were determined. Histopathological evaluation of lung tissue was performed using hematoxylin and eosin (H&E), and periodic acid-schiff (PAS) staining. Th1/Th2 cytokine mRNA expression was analyzed using the 2 -ΔΔCt method. Results Treatment with AQs decreased inflammatory cell counts and production of Th2 cytokines (IL-4, IL-5 and IL-13) in BALF, and OVA-specific IgE in serum. In contrast,Th1 cytokine IFN- γ production in BALF was promoted. AQs also decreased mRNA expression of Th1/Th2 cytokine in lung tissue. Histological studies demonstrated that AQs substantially inhibited OVA-induced cellular infiltration, mucus hypersecretion and goblet cell hyperplasia in the lung. Conclusions These findings demonstrated the inhibitory effects of AQs, derived from C. occidentalis, on OVA-induced allergic asthma in mice. The results suggest a promising ethnopharmacological use for AQs in patients with asthma.
研究领域:
药理学
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免疫学
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民族药理学
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呼吸医学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2021
·
IF 5.34
Xiaohan Wei,Baoping Zhang,Xiao Liang,Changshun Liu,Ting Xia,Yingjie Xie,Xue Deng,Xiaomei Tan
ABSTRACT Background Allergic rhinitis (AR) is an inflammatory, immunoglobulin E (IgE)-mediated disease characterized by the typical symptoms of sneezing, rhinorrhea , nasal itching , and congestion. Higenamine (HG) is a plant-based alkaloid, possesses a wide range of activities, including vascular and tracheal relaxation, antioxidative, antiapoptotic , anti-inflammatory, and immunomodulatory activities. So far, the effect and the underlying mechanism of HG on AR have not been studied. Hypothesis/Purpose The purpose of this study was to evaluate the effects of HG on AR and investigate its underlying mechanism. Methods The effects of HG on AR were evaluated in an ovalbumin-induced AR mouse model. Network pharmacology-based methods such as target prediction, protein-protein interaction (PPI) network analysis, pathway analysis, and molecular docking were used to identify the likely HG targets. Finally, we validated the mechanism of action of HG through its effects on these targets in human nasal epithelial cells (HNEpCs). Results Oral administration of 30, 60, and 120 mg/kg HG significantly alleviated rubbing and sneezing in AR mice and attenuated histopathological changes in the lung and nasal tissues . Additionally, HG reduced the levels of IgE, histamine, and IL-4 in the serum of AR mice, and regulated imbalance in Th1/Th2 cells. Using network pharmacology-based methods, we identified 29 HG targets related to AR. These targets are mainly involved in the PD-L1, relaxin, estrogen, HIF-1, Th1 and Th2 cell differentiation , T cell receptor , and the Th17 cell differentiation signaling pathways . Molecular docking showed that HG may well be suited to the receptor binding pockets of key target AKT1 , EGFR, c-Jun, NOS2 , and JAK2 . In HNEpCs, HG inhibited the histamine-induced mRNA expression and secretion of interleukin (IL)-6, and IL-8, as well as the expression of MUC5AC and the phosphorylation of NF-κB. Moreover, HG affected the changes of AKT1, EGFR, c-Jun, iNOS, and JAK2 induced by histamine. Conclusion Overall, our results suggest that HG may alleviate AR by activating AKT1 and suppressing the EGFR/JAK2/c-JUN signaling. HG, therefore, has great potential as a therapeutic agent for the treatment of AR.
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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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Xinxin Hou,Zhaozhou Zhang,Wanqing Chen,Jinming Li,Xiangxiang Zhu,Mingjie Li,Xiaoqi Guan,Haidong Guo,Yanlei Ma,Ling Zhao
Altered gut microbiota has evidenced to be associated with colitis and colonic tumorigenesis, however bacteria-driven mechanism underlying inflammation-related colon pathologies remains undetermined. This study identifies a previously overlooked genus, Megasphaera , is highly abundant in inflammatory bowel diseases (IBD) and colorectal cancer (CRC) cohorts. A Megasphaera species, M. elsdenii reshapes colonic immunity by triggering dendritic cell (DC)-mediated Th1 and Th17 inflammation. Mechanistically, M. elsdenii and its lipopolysaccharide triggers DC activation via TLR4/NF-κB/IRF4 pathway. Accordingly, in Tlr4 −/− mice, M. elsdenii colonization cannot expand colonic infiltration of DCs and fails to induce Th1 and Th17 responses in. In a Shanghai CRC cohort with a 100% detective rate for Megasphaera , the species of Megasphaera significantly dominated in early onset CRC patients (<50 years old) rather than late-onset CRC (≥50 years old). M. elsdenii and M. elsdenii -enriched microbiota exacerbate colonic inflammation and tumorigenesis in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine colitis-associated cancer model. Taken together, this study uncovers a pathogenic role of Megasphaera in developing colonic tumorigenesis via activating DC-mediated inflammation.
研究领域:
微生物学
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免疫学
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肿瘤学
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胃肠病学
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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 ETHNOPHARMACOLOGY
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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 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
·
2024
·
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
危险品化学品经营许可证（带存储）