Frontiers in Immunology
·
2022
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IF 8.786
ZhengQing Yu,Ke He,WanDi Cao,Muhammad Tahir Aleem,RuoFeng Yan,LiXin Xu,XiaoKai Song,XiangRui Li
Caused by Toxoplasma gondii , toxoplasmosis has aroused great threats to public health around the world. So far, no effective vaccine or drug is commercially available, and the demands for a safe and effective therapeutic strategy have become more and more urgent. In the current study, we constructed a DNA vaccine encoding T. gondii ribosomal P2 protein (TgP2) and denoted as TgP2-pVAX1 plasmid. To improve the immunoprotection, nanomaterial poly-lactic- co -glycolic acid (PLGA) and chitosan were used as the delivery vehicle to construct TgP2-pVAX1/PLGA and TgP2-pVAX1/CS nanospheres. Before vaccinations in BALB/c mice, TgP2-pVAX1 plasmids were transiently transfected into Human Embryonic Kidney (HEK) 293-T cells, and the expression of the eukaryotic plasmids was detected by laser confocal microscopy and Western blotting. Then the immunoprotection of naked DNA plasmids and their two nano-encapsulations were evaluated in the laboratory animal model. According to the investigations of antibody, cytokine, dendritic cell (DC) maturation, molecule expression, splenocyte proliferation, and T lymphocyte proportion, TgP2-pVAX1 plasmid delivered by two types of nanospheres could elicit a mixed Th1/Th2 immune response and Th1 immunity as the dominant. In addition, TgP2-pVAX1/PLGA and TgP2-pVAX1/CS nanospheres have great advantages in enhancing immunity against a lethal dose of T. gondii RH strain challenge. All these results suggested that TgP2-pVAX1 plasmids delivered by PLGA or chitosan nanomaterial could be promising vaccines in resisting toxoplasmosis and deserve further investigations and applications.
研究领域:
免疫学
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分子生物学
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纳米技术
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寄生虫学
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疫苗学
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产品关联
DOI
PubMed
高影响因子
Cancer Communications
·
2023
·
IF 16.2
Shujie Chen,Lina Fan,Yifeng Lin,Yadong Qi,Chaochao Xu,Qiwei Ge,Ying Zhang,Qiwen Wang,Dingjiacheng Jia,Lan Wang,Jianmin Si,Liangjing Wang
Background The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is not well explored. Here, we elucidated the functional role of Bifidobacterium adolescentis ( B.a ) on CRC and investigated its possible mechanism on the manipulation of cancer-associated fibroblasts (CAFs) in CRC. Methods Different CRC animal models and various cell line models were established to explore the function of B.a on CRC. The single-cell RNA sequencing (scRNA-seq) or flow cytometry was used to detect the cell subsets in the TME of CRC. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), or immunofluorescence staining were performed to examine the activation of Wnt signaling and growth arrest specific 1 (GAS1) on CD143 + CAFs. Chromatin immunoprecipitation quantitative real-time PCR (CHIP-qPCR) was performed to investigate the regulation of transcription factor 4 (TCF4) on GAS1. Multi-immunofluorescence assay examined the expression level of CD143 and GAS1 on tissue microarray. Results We found that B.a abundance was significantly reduced in CRC patients from two independent cohorts and the bacteria database of GMrepo. Supplementation with B.a suppressed Apc Min/+ spontaneous or AOM/DSS-induced tumorigenesis in mice. scRNA-seq revealed that B.a facilitated a subset of CD143 + CAFs by inhibiting the infiltration of Th2 cells, while promoting the TNF-alpha + B cells in TME. CD143 + CAFs highly expressed GAS1 and exhibited tumor suppressive effect. Mechanistically, GAS1 was activated by the Wnt/β-catenin signaling in CD143 + CAFs. B.a abundance was correlated with the expression level of CD143 and GAS1. The level of CD143 + CAFs predicted the better survival outcome in CRC patients. Conclusions These results highlighted that B.a induced a new subset of CD143 + CAFs by Wnt signaling-regulated GAS1 to suppress tumorigenesis and provided a novel therapeutic target for probiotic-based modulation of TME in CRC.
研究领域:
癌症生物学
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微生物学
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分子生物学
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细胞生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
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IF 4.4
Huiyuan Zhang,Quanbin Li,Yaxing Li,Jianhua Guan,Kaidi Li,Yunlong Chen
Background: Atopic dermatitis (AD) is among the most frequently encountered skin diseases, bothering a considerable number of patients. Today, corticosteroids and antihistamines are among the numerous drugs applied for the therapy of AD. However, lengthy use of them contributes to side effects, such as physiological changes in skin. As an alternative and supplementary therapy, traditional Chinese medicine has become a trend for AD treatment. Huang-Lian-Jie-Du decoction (HLJDD), a renowned herbal formula has been employed to treat inflammatory diseases such as AD. However, its role in regulating immunity in AD remains unclear. The object of this study was to elucidate the efficacy of HLJDD and reveal the implicit mechanism from an immunological perspective in AD-like mice.Methods: In brief, 1-chloro-2,4-dinitrobenzene (DNCB) for the sensitization phase (1% DNCB) and stimulation phase (1.5% DNCB) were applied for BALB/c mice. HLJDD and dexamethasone (DXMS) were administered orally to the mice. Mice skin and spleens were collected to evaluate the efficacy of HLJDD. 16S rRNA sequencing was applied to evaluate the commensal microbiota changes in skin and fecal. In vitro, spleen CD4+ T cells and bone marrow-derived mast cells (BMMCs) were co-cultured to explore the modulation of HLJDD in T helper (Th) cells phenotyping.Results: HLJDD showcased a substantial amelioration in skin through the upregulation of FLG, LOR, AQP3, and reducing scratching behaviors in AD-like mice, Also, the quantity of infiltrated mast cells (MCs), pruritus-related mRNA were decreased. In addition, the expression of OX40/OX40L was decreased by HLJDD, which was critical in Th-cell phenotyping. With the treatment of HLJDD, Th1/Th2 and Th17/Treg ratios in AD-like mice became balanced. The structure of commensal microbiota in AD-like mice was affected by HLJDD. HLJDD could also improve the imbalance of Th17/Treg in vitro.Conclusion: HLJDD could improve the symptoms of AD-like mice by alleviating the scratching behaviors via decreased Th2 and pruritus-related mRNA expression. HLJDD also enhanced the relative diversity of skin microbiota and changed the structure of intestinal microbiota. An in-depth study found that HLJDD could balance the ratio of Th1/Th2, Th17/Treg in AD-like mice, and Th17/Treg in vitro by regulating the OX40/OX40L signaling pathway.
研究领域:
免疫学
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皮肤病学
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中医
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微生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2021
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IF 6.953
Teng Wang,Chen Shen,Feng Guo,Yuqin Zhao,Jie Wang,Kunlai Sun,Bin Wang,Yan Chen,Yin Chen
A polysaccharide, CSL-0.1, was isolated from the medicinal lichen, Usnea longissima . CSL-0.1 was a neutral rhamnose-containing glucogalactomannan with a molecular weight of 7.86 × 10 4 Da. The polysaccharide had a core mannan structure with (1 → 6)-α- d -Man p units as the main chain and was substituted at the O -2 positions with side chains containing (1 → 2)-α- d -Man p residue, [3)-α-Glc p (1 → 4)-α-Glc p (1→] and 6- O -substituted β- d -Gal f units. 2- O - and 2,3-di- O -substituted Rha p units. The effects of CSL-0.1 on intestinal immunity and antioxidant activity were evaluated. CSL-0.1 increased the spleen and thymus indices in a dose-dependent manner and conferred immunomodulation on reversing the Th1/Th2-related cytokine imbalance in cyclophosphamide (CP)-induced immunosuppressed mice. CSL-0.1 could also enhance the levels of secretory immunoglobulin A in CP-injected mice. Additionally, the antioxidant levels in the liver and intestine of the mice were increased 20%–50% after intragastric injection by CSL-0.1.
研究领域:
免疫学
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药理学
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生物化学
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药物化学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
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IF 6.656
Zhonghao Li,Qinmei Sun,Qingyang Liu,Xinru Mu,Hui Wang,Han Zhang,Fenfen Qin,Qisheng Wang,Dengyun Nie,Anlong Liu,Qian Li,Jianjian Ji,Yongwei Jiang,Shengfeng Lu,Qian Wang,Zhigang Lu
Background Opioids are widely used in clinical practice. However, their long-term administration causes respiratory depression , addiction, tolerance, and severe immunosuppression . Traditional Chinese medicine (TCM) can alleviate opioid-induced adverse effects. Compound 511 is particularly developed for treating opioid addiction, based on Jiumi Liangfang, an ancient Chinese drug treatment and rehabilitation monograph completed in 1833 A.D. It is an herbal formula containing eight plants, each of them contributing to the overall pharmacological effect of the product: Panax ginseng C. A. Meyer (8.8%), Astragalus membranaceus (Fisch.) (18.2%), Datura metel Linn. (10.95%), Corydalis yanhusuo W. T. Wang (14.6%), Acanthopanar gracilistμlus W. W. Smith (10.95%), Ophiopogon japonicus (Linn. f.) Ker-Gawl. (10.95%), Gynostemma pentaphyllum (Thunb.) Makino (10.95%), Polygala arvensis Willd. (14.6%). This formula effectively ameliorates opioid-induced immunosuppression. However, the underlying mechanism remains unclear. Purpose To reveal the effects of Compound 511 on the immune response of morphine-induced immunosuppressive mice and their potential underlying molecular mechanism. This study provides information for a better clinical approach and scientific use of opioids. Methods Immunosuppression was induced in mice by repeated morphine administration. Th1/Th2/Th17/Treg cell levels were measured using flow cytometry. Splenic transcription factors of Th1/Th2/Th17/Treg and outputs of the regulatory PI3K/AKT/mTOR signaling pathway were determined. Subsequently, methicillin-resistant Staphylococcus aureus (MRSA) was administered intranasally to morphine-induced immunosuppressive mice pretreated with Compound 511. Their lung inflammatory status was assessed using micro-computer tomography (CT), hematoxylin and eosin (H&E) staining, and enzyme-linked immunosorbent assay (ELISA). Results Compared to morphine, Compound 511 significantly decreased the immune organ indexes of mice, corrected the Th1/Th2 and Treg/Th17 imbalance in the immune organs and peripheral blood, reduced the mRNA levels of FOXP3 and GATA3 , and increased those of STAT3 and T-bet in the spleen . It improved immune function and reduced MRSA-induced lung inflammation. Conclusion Compound 511 ameliorates opioid-induced immunosuppression by regulating the balance of Th1/Th2 and Th17/Treg via PI3K/AKT/mTOR signaling pathway. Thus, it effectively reduces susceptibility of morphine-induced immunosuppressive mice to MRSA infection .
研究领域:
药理学
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免疫学
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微生物学
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中药学
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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 Functional Foods
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2021
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IF 4.451
Xiaoyan Su,Ming Zhao,Xinyu Fu,Xiaodan Ma,Wei Xu,Songhua Hu
Polysaccharides from Rubus chingii Hu fruits (RFPs) were extracted, purified, characterized and investigated for immunomodulatory activity. Results indicated that RFPs were heteropolysaccharides with molecular weight of 51.7 kDa and contained carbohydrate contents of 96.83%. RFPs with characteristic absorptive peaks of polysaccharide structure and α-configuration were composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose and fucose with a molecular ratio of 0.08:0.17:0.16:0.48:5.73:1.00:1.79:0.03. RFPs promoted splenocyte proliferation, NO release, cytokine production and intracellular Ca 2+ concentration. The mechanism underlying splenocyte activation by RFPs was elucidated by RNA-Seq, in which 2214 differentially expressed genes (DEGs), 2030 GO terms and 92 KEGG pathways were identified. RFPs were further proved to induce a balanced Th1/Th2/Th17 response pattern through MAPK, NF-κB, Jak-STAT and Calcium signaling pathways in splenocytes. These findings provided a fundamental basis for the further application of RFPs as immunomodulators in food and medicine.
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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生物化学
✓ 已验证
DOI
高影响因子
Acta Biomaterialia
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2025
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IF 9.6
Pengtong Li,Chenxi Huang,Yijie He,Xinyu Lei,Xiaoyan Shen,Jialin Xu,Yunfei Mo,Xiuhong Sun,Ling Zheng,Yuqing Niu
The earliest tissue-engineered vascular grafts (TEVGs) applied clinically are biodegradable scaffolds laden with bone marrow mononuclear cells (BMCs). However, the inability to control BMCs fate after transplantation severely restricts their clinical use. To overcome this limitation, we developed a regenerative TEVG and investigated its role in modulating the immune microenvironment at arterial defects sites to enhance tissue regeneration. This TEVG was fabricated from a degradable elastomeric nanofiber scaffold combined with rBMCs, which had been induced to differentiate into regenerative M2 macrophages through in vitro culture. The resulting M2-derived extracellular matrix (ECM) dynamically modulated scaffold elasticity to match the biomechanical environment of the implantation site. When implanted into a rat abdominal aortic (rAA) defect model, the TEVGs, serving as interpositional artery grafts, could maintain the patency of abdominal artery blood circulation in rats and gradually transform into mature abdominal arteries within 12 months. However, the implanted rBMCs migrated away shortly after implantation. Instead, the scaffolds were initially repopulated by rat monocytes and subsequently gradually replaced by rat endothelial cells (ECs) and smooth muscle cells (SMCs). Further research revealed that the implanted M2 macrophages secrete IL-10 and IL-4, activating CD4 + T cells and initiating the Th2 pathway. IL-4 derived from Th2 cells sustained the M2 macrophages phenotype, forming a positive feedback loop that boosted the regenerative microenvironment-key to restoring arterial function. These findings suggest that integrating BMCs into vascular grafts and regulating the extracellular microenvironment may offers a practical and efficient strategy for treating damaged and diseased arteries. Statement of Significance The earliest clinically applied tissue-engineered vascular grafts (TEVGs) are biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs), but the uncontrolled fate of BMCs after transplantation restricts their clinical use. This study developed a regenerative TEVG combining a degradable elastic nanofiber scaffold with in vitro -induced M2 macrophages. In a rat model, the TEVG maintained arterial patency and transformed into mature arteries within 12 months by activating an M2/Th2 immune positive feedback loop, offering a new strategy for arterial injury treatment.
研究领域:
生物医学工程
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组织工程
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免疫学
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再生医学
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血管生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
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IF 5.6
Chengchen Pang,Bei Yuan,Keyun Ren,Haitao Xu,Kunying Nie,Chunlei Yu,Zhanli Liu,Yanyan Zhang,Sibel A. Ozkan,Qingqing Yang
In preparing monoclonal antibodies by hybridoma cell technology, the quality of B lymphocytes used for cell fusion directly affects the sensitivity of monoclonal antibodies. To obtain B-lymphocytes producing high-quality specific antibodies for cell fusion during the immunization phase of the antigen, we prepared a TH2-Cell stimulatory delivery system as a novel adjuvant. Astragalus polysaccharide has a good ability to enhance antigenic immune response, and it was encapsulated in biocompatible materials PLGA as an immunostimulatory factor to form the delivery system (APS-PLGA). The preparation conditions of APSP were optimized using RSM to attain the highest utilization of APS. Immunization against ZEN-BSA antigen using APSP as an adjuvant to obtain B lymphocytes producing ZEN-specific antibodies for cell fusion. As results present, APSP could induce a stronger TH2 immune response through differentiating CD4 T cells and promoting IL-4 and IL-6 cytokines. Moreover, it could slow down the release efficiency of ZEN-BSA and enhance the targeting of ZEN-BSA to lymph nodes in vivo experiments. Ultimately, the sensitivity of mouse serum ZEN-specific antibodies was enhanced upon completion of immunization, indicating a significant upregulation of high-quality B lymphocyte expression. In the preparation of monoclonal antibodies, the proportion of positive wells for the first screening was 60%, and the inhibition rates of the antibodies were all similar (>50%). Then we obtained the ZEN monoclonal antibody with IC50 of 0.049 ng/mL, which was more sensitive than most antibodies prepared under conventional adjuvants. Finally, a TRFIAS strip assay was preliminarily established with a LOD value of 0.246 ng/mL.
研究领域:
免疫学
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生物技术
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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
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
Scientific Reports
·
2022
·Vol. 12
·期 1
·1-15
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IF 4.996
Dong Hao,Feng Chenjie,Cai Xiyunyi,Hao Yuanyuan,Gu Xinyue,Cai Lei,Wu Shuting,Chen Jiamin,Liu Zhou,Xie Wen,Lu Xuanren,Qian Hongfa,Liu Yulin,Cao Yiming,Zhu Junlin,Xu Jiayi,Zhou Yanjie,Ma Shuangyu,Yang Sha,Shi Yufeng,Yu Haojiang,Shi Minjie,Wang Yurong,Gu Harvest F.,Fan Lei,Wu Liang
7-Met, a derivative of soybean isoflavone, is a natural flavonoid compound that has been reported to have multiple signaling pathways regulation effects. This study investigated the therapeutic effects of 7-Met on mice with atopic dermatitis induced by fluorescein isothiocyanate (FITC), or oxazolone (OXZ). 7-Met ameliorated FITC or OXZ-induced atopic dermatitis symptoms by decreasing ear thickness, spleen index, mast cell activation, neutrophil infiltration and serum IgE levels in female BALB/c mice. In FITC-induced atopic dermatitis mice, 7-Met reduced Th1 cytokines production and regulated Th1/Th2 balance by downregulating the secretion of thymic stromal lymphopoietin (TSLP) via inactivation of the NF-κB pathway. In OXZ-induced atopic dermatitis, 7-Met functioned through the reduction of Th17 cytokine production. Our study showed that 7-Methoxyisoflavone alleviated atopic dermatitis by regulating multiple signaling pathways and downregulating chemokine production.
研究领域:
免疫学
·
药理学
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皮肤病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
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IF 8.2
Yueyue Meng,Huiyu Zhu,Lingyu Han,Zhe Xu,Yu Zou,Kun Ma,Tingting Li
Cow's milk is one of the “big eight” most common allergenic foods, and β-lactoglobulin and α-Lactalbumin in whey protein are two major allergens of cow's milk protein. An effective strategy for reducing the allergenicity of whey protein is needed. In the present study, protein-EGCG complexes were obtained through non-covalent interactions between untreated or sonicated whey protein isolate (WPI) and epigallocatechin gallate (EGCG), and the allergenicity of complexes was assessed in vivo. The results showed that SWPI-EGCG complex possesses low allergenicity in BALB/c mice. As compared with untreated WPI, SWPI-EGCG complex had less effect on the body weight and organ indexes. Moreover, SWPI-EGCG complex could alleviate the WPI induced allergic reactions and intestinal damage of mice by decreasing the secretion of IgE, IgG, histamine, mMCP-1, modulating the balance of Th1/Th2 and Treg/Th17 response, and increasing the diversity of intestinal flora and the relative abundances of probiotic bacteria. These findings indicate that the interaction of sonicated WPI with EGCG could reduce the allergenicity of WPI, which could provide a new strategy for reducing food allergenicity.
研究领域:
食品科学
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免疫学
·
微生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
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IF 4.3
Fangfang Min,Jielun Hu,Tao Huang,Yousheng Huang,Shaoping Nie,Tao Xiong,Mingyong Xie
Lactobacillus ( L. ) casei NCU011054 isolated from infant feces has been proven to be a potential probiotic in vitro . The present study aimed to investigate the effects of L. casei NCU011054 on the immune response and gut microbiota in cyclophosphamide (CP)-induced immunosuppression mice. Results indicated that L. casei NCU011054 could increase the levels of mucin (Muc2) and tight junction proteins (ZO-1, occludin and claudin-1). Moreover, L. casei NCU011054 was found to upregulate TLRs/NF-κB pathway (TLR-2, TLR-4, TLR-6, p65 and NF-κB) and two transcription factors (T-bet and GATA-3) mRNA levels, and enhance the number of CD4 + T cells. Th1-related cytokines (IL-12p70, IFN-γ and TNF-α) and Th2-related cytokines (IL-2, IL-4, IL-6 and IL-10) significantly increased after L. casei NCU011054 treatment. More importantly, L. casei NCU011054 increased the ratio of T-bet to GATA-3 and IFN-γ to IL-4. Apart from these, L. casei NCU011054 remodeled gut microbiota and modulated gut metabolites in CP-induced immunosuppressed mice. The correlation analysis showed that Lactobacillus upregulated by L. casei NCU011054 was positively correlated with TLRs/NF-κB pathway, and the ratio of T-bet to GATA-3 and IFN-γ to IL-4. All findings revealed that L. casei NCU011054 could improve intestinal immune dysfunction and modulate Th1/Th2 balance via TLRs/NF-κB pathway in CP-induced immunosuppressed mice.
研究领域:
免疫学
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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）