Emergency Medicine International
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2021
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IF 1.112
Chen Zongyun,Lin Bixia,Ding Fadian,Hong Xiaoping,Chen Hongbin,Deng Yu,Liu Qicai,Ye Xiaoyi,Zeng Kai
Introduction. The advances in cerebral ischemia treatment have resulted in a larger proportion of patients get the benefits of rebuilding blood flow to the brain. Then, ischemia-reperfusion injury has emerged as a new essential problem. Dectin-1 plays an important role in cerebral ischemia-reperfusion injury by regulating the function of immune cells. Methods. C57BL/6 was blindly divided into four groups including the sham-operated group and the three different kinds of middle cerebral artery occlusion (MCAO) groups (after 6 hours, 12 hours, and 24 hours after plug removal). The protein expression levels of dectin-1, proapoptosis molecule, and antiapoptosis molecule were measured by using western blot analysis. The brain tissue was analyzed by flow cytometry to detect the M1 macrophage levels. Results. The correlation analysis of dectin-1 and infarct areas showed that there was an obviously positive correlation in between them (R = 0.9603). Dectin-1, cleaved caspase-3, and Bax increased, while antiapoptosis molecule, Bcl-2, decreased at three appropriate time points (after 6 hours, 12 hours, and 24 hours). The level of M1 macrophages in the experimental group increased after ischemia-reperfusion injury compared to the control group. Conclusions. The high expression level of dectin-1 may affect M1 macrophage polarization and brain cell apoptosis in cerebral ischemia-reperfusion injury.
研究领域:
神经科学
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免疫学
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分子生物学
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PubMed
高影响因子
EUROPEAN JOURNAL OF PAIN
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2024
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IF 3.5
Hao-Nan Zheng,Yu-Ru Zhi,Yang-Shuai Su,Jin-Yan Jiang,Hao-Zhou Zhang,Feng Cao,Yun Wang,Yan Chi,Ying Zhang
Background Visceral hypersensitivity is considered the core pathophysiological mechanism that causes abdominal pain in patients with irritable bowel syndrome (IBS). Fungal dysbiosis has been proved to contribute to visceral hypersensitivity in IBS patients. However, the underlying mechanisms for Dectin-1, a major fungal recognition receptor, in visceral hypersensitivity are poorly understood. This study aimed to explore the role of Dectin-1 in visceral hypersensitivity and elucidate the impact of Dectin-1 activity on the function of transient receptor potential vanilloid type 1 (TRPV1). Methods Visceral hypersensitivity model was established by the intracolonic administration of 0.1 mL TNBS (130 μg/mL in 30% ethanol) in the male mice. Fluconazole and nystatin were used as fungicides. Laminarin, a Dectin-1 antagonist and gene knockout ( Clec7a −/− ) mice were used to interrupt the function of Dectin-1. Colorectal distension-electromyogram recording was performed to assess visceral sensitivity. Immunostaining experiment was performed to determine the localization of Dectin-1 in dorsal root ganglion (DRG) neurons. Calcium imaging study was performed to assay TRPV1-mediated calcium influx in acutely dissociated DRG neurons. Results Pretreatment with fungicides, administration of laminarin or genetic deletion of Clec7a alleviated TNBS-induced visceral hypersensitivity in male mice. The expression of Dectin-1 was upregulated in the DRG and colon of TNBS-treated mice. Colocalization of Dectin-1 and TRPV1 was observed in DRG neurons. Importantly, pretreatment with curdlan, a Dectin-1 agonist, increased TRPV1-mediated calcium influx. Conclusions Dectin-1 contributes to visceral hypersensitivity in IBS or in inflammatory bowel disease in remission and activation of Dectin-1 induces TRPV1 sensitization. Significance Statement This work provides direct evidence for the functional regulation of TRPV1 channel by Dectin-1 activity, proposing a new mechanism underlying TRPV1 sensitization. Control of intestinal fungi might be beneficial for the treatment of refractory abdominal pain in patients with IBS or IBD in remission.
研究领域:
胃肠病学
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免疫学
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疼痛研究
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神经科学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
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IF 10.7
Kaiping Wang,Yuxuan Liu,Zeming Zhang,Ziming Zheng,Wenqi Tang,Wangtianzi Teng,Xu Mu,Jinglin Wang,Yu Zhang
Lentinan (LNT), a natural polysaccharide, has been reported to exhibit immunomodulatory effects in the intestine after oral administration. Herein, we aimed to investigate the lymphatic transport of LNT in Peyer's patches (PPs) by traceable fluorescent labeling and to explore whether/how LNT contacts related immune cells. Near-infrared imaging confirmed the absorption of LNT in the small intestinal segment and its accumulation within PPs after oral administration. Subsequently, tissue imaging confirmed that M cells are the main cells responsible for transporting LNT to PPs, and an M cell model was established to explore the involvement of Dectin-1 in the absorption process. Systematic in vitro and in vivo studies revealed that the Dectin-1 further mediates the uptake of LNT by mononuclear phagocytes in PPs. Moreover, LNT can promote the proliferation and differentiation of mononuclear phagocytes, thereby activating immune responses. In summary, this study elucidates the pharmacokinetic mechanisms by which LNT exerts oral immunomodulatory effects, providing a theoretical basis for the development and application of other polysaccharides.
研究领域:
免疫学
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药理学
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胃肠病学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Xiaoli Ling,Zhipeng Tian,Dong Chen,Yujia Zhang,Ziyan Dong,Dan He,Jiayu Li,Zhidi He,Jiaxin Li,Fang Chen,Qin He,Man Li
Self-adjuvanted vaccine delivery platforms possess potential for targeted delivery of antigens and initiation of potent immune responses. Although aluminum-containing adjuvants have been approved and widely used in human vaccines, their effectiveness in inducing Th1-type immune responses is far from satisfactory. To facilitate antigen delivery and activate potent antitumor immune responses, a self-adjuvanted nanovaccine (CPBG-Al@OVA) is constructed by functionalizing aluminum hydroxide with β-1,3-glucan, which recognizes pattern recognition receptors via Dectin-1. Carboxymethyl-phosphorylated β-1,3-glucan (CPBG) has been synthesized and optimized to achieve superior adjuvanticity while maintaining water solubility. CPBG then self-assembles with aluminum hydroxide and the targeted antigen, leading to the formation of a nanovaccine CPBG-Al@OVA. Owing to the favorable nanoscale size distribution, CPBG-Al@OVA effectively drains to the lymph nodes and is internalized by antigen-presenting cells (APCs) through Dectin-1-mediated endocytosis, activating the Syk and Raf1 signaling pathways and leading to upregulated TNFSF15 and OX40L expression to activate APCs. Following immunization, CPBG-Al@OVA activates potent CD8 + T cell and humoral responses to inhibit tumor growth. Notably, mice vaccinated with CPBG-Al@OVA showed extended survival, with more than 70 % of the mice surviving for over 50 days post-tumor challenge. Moreover, the CPBG-Al nanoparticle also possesses personalized immune-activating capacity by encapsulating tumor lysate as an antigen, specifically suppressing tumor growth. This strategy synergizes the adjuvant effects of aluminum and β-1,3-glucan, offering a platform for self-adjuvanted nanovaccine design with significant clinical translational potential.
研究领域:
免疫学
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癌症研究
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疫苗学
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分子生物学
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PubMed
高影响因子
IMMUNITY
·
2025
·Vol. 58
·期 7
·1811-1829
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IF 26.3
Ding Qiu,Shuishen Zhang,Chanyan Huang,Xinying Wang,Jianping Deng,Haiyang Sun,Bingbing Feng,Ying Tan,Kaile Ji,Shaoting Xu,Xiaoqi Ye,Chao Cheng,Shigeru Kakuta,Yoshiyuki Adachi,Yoichiro Iwakura,Shuai Wang,Shaowei Dong,Ce Tang
Dectin-1 ( Clec7a ), a C-type lectin receptor for β-glucans, is critical in host defense against fungal infections and has been implicated in allergic responses, yet its role in pulmonary fibrosis remains unclear. In this study, we reveal that bleomycin-induced pulmonary fibrosis was suppressed in Dectin-1-deficient mice, mediated by interactions with the commensal lung fungus Engyodontium . Dectin-1 was predominantly expressed on alveolar macrophages (AMs), correlating with fibrosis severity in both humans and mice. Dectin-1 deficiency reduced Arginase-1 and TGF-β-producing AMs and profibrotic factor expression. Mechanistically, Dectin-1 signaling promoted quiescent AM differentiation into profibrotic AMs via the Raf1-dependent pathway, bypassing CARD9 signaling and mono-macrophage chemotactic recruitment. Therapeutic targeting of Dectin-1 with laminarin or Raf1 inhibitors attenuated fibrosis in mice and reduced profibrotic factors in human AMs and fibroblasts. These findings highlight the Dectin-1-Raf1 axis as a key regulator of pulmonary fibrosis and a promising therapeutic target for fibrotic diseases.
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高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Junsong Jing,Yi Sun,Yiyang Shui,Junyi Wang,Wenjing Ye,Ranran Chen,Lianhao Wu,Lijuan Xing,Rongrong Huang,Ting Zhou,Wenwen Zhu,Yueguo Wu,Sheng Zhang,Jing Shi,Yuanyuan Li,Yan Liu,Zhenqiang You
Background Viral pneumonia is an infection of the lungs caused by numerous different viruses, which can lead to severe respiratory distress and even life-threatening conditions. In the absence of specific treatments for viral pneumonia, natural traditional medicines offer an alternative in terms of innovative drug therapies. Morus alba L. (common name mulberry leaf) is a Chinese medicine that has been used clinically as an antiviral. Purpose The therapeutic effect of M. alba on viral pneumonia was investigated along with its mechanism of action. Methods Network pharmacology and molecular docking were used to analyze the mechanism of action of M. alba in the treatment of viral pneumonia. Histology, immunofluorescence, Western blotting, qPCR, and flow cytometry were used to evaluate the protective effect of MLE (the ethanol extract of Morus alba L. ) on PR8 (A/Puerto Rico/8/1934 H1N1, a murine lung-adapted influenza A virus strain)-induced viral pneumonia. SiRNA was used to validate the relationship between the therapeutic effects of MLE on viral pneumonia and the target Syk (a crucial non-receptor tyrosine kinase). Results MLE alleviated PR8-induced viral pneumonia by reducing inflammatory factor expression in the lungs, decreasing NF-κB pathway activation, slowing oxidative damage in the lungs, and inhibiting lung tissue cell apoptosis. Meanwhile, MLE for viral pneumonia was significantly associated with Syk targets. Notably, knockdown of the Syk gene not only reduced the therapeutic effect of MLE, but also suppressed PR8-induced viral pneumonia. Conclusion MLE can alleviate PR8-induced viral pneumonia through inhibiting the Dectin-1/Syk pathway.
研究领域:
药理学
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分子生物学
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病毒学
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PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2025
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IF 8
Fangcheng Hu,Xingyuan Liu,Chunping Chen,Yushan Liu,Xiaotong Xu,Lin Han,Caian He,Min Wang
The clinical translation of urolithin A (UA), an ellagitannin-derived metabolite with antioxidant and mitophagy-inducing properties, is hampered by its poor solubility, limited stability, and low oral bioavailability. To address these limitations, we developed a core-shell nanoplatform (UA@ZIF-8@CMG) comprising a ZIF-8 core for efficient encapsulation and a carboxymethyl β-glucan (CMG) shell for enhanced stability and potential targeting. The optimized formulation exhibited a high drug-loading capacity (12.65 %), markedly improved UA stability, and demonstrated pH-responsive release, with minimal leakage (22 %) under simulated gastric conditions followed by sustained release in the intestinal environment. In vitro studies revealed reduced cytotoxicity and a dual cellular uptake mechanism, involving putative Dectin-1-mediated endocytosis in macrophages and nonspecific uptake in intestinal cells. This uptake profile resulted in superior preservation of mitochondrial membrane potential and more effective ROS scavenging compared with free UA. The key innovation of this system lies in the synergistic ZIF-8@CMG architecture, which integrates robust protection, controlled release, and cell-type-specific uptake, thereby distinguishing it from previously reported delivery platforms. Collectively, this work presents a translatable strategy to enhance UA bioavailability and therapeutic performance, underscoring its promise for both nutraceutical and pharmaceutical applications.
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高影响因子
GLYCOBIOLOGY
·
2021
·Vol. 31
·期 8
·931-946
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IF 4.313
Li Chunxia,Palma Angelina S,Zhang Pengtao,Zhang Yibing,Gao Chao,Silva Lisete M,Li Zhen,Trovão Filipa,Weishaupt Markus,Seeberger Peter H,Likhosherstov Leonid M,Piskarev Vladimir,Yu Jin,Westerlind Ulrika,Chai Wengang
Glycan microarrays have played important roles in detection and specificity assignment of glycan recognition by proteins. However, the size and diversity of glycan libraries in current microarray systems are small compared to estimated glycomes, and these may lead to missed detection or incomplete assignment. For microarray construction, covalent and noncovalent immobilization are the two types of methods used, but a direct comparison of results from the two platforms is required. Here we develop a chemical strategy to prepare lipid-linked probes from both naturally derived aldehyde-terminating and synthetic amino-terminating glycans that addresses the two aspects: expansion of sequence-defined glycan libraries and comparison of the two platforms. We demonstrate the specific recognition by plant and mammalian lectins, carbohydrate-binding modules and antibodies and the overall similarities from the two platforms. Our results provide new knowledge on unique glycan-binding specificities for the immune receptor Dectin-1 toward β-glucans and the interaction of rotavirus P[19] adhesive protein with mucin O-glycan cores.
研究领域:
生物化学
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免疫学
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分子生物学
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PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2021
·Vol. 109
·期 12
·2506-2515
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IF 4.396
Jing Wei Jin,Min Zhi Rong,Ming Qiu Zhang,Wing-Leung Wong
β-1,3-D-glucan has been reported to have a series of bioactivities including antitumor, antimicrobial, anti-inflammatory and antioxidative effects; however, its insolubility in neutral aqueous solution significantly restricts the potential application in biological and medicine fields. Herein, a water-soluble aminated β-1,3-D-glucan (AG) was synthesized and the anti-inflammatory effect, cytotoxicity and plasmid DNA (pDNA) binding capacity of AG, serum stability, the particle sizes and zeta potentials of AG/pDNA nanocomposites, and the transfection efficiency and mechanism of action were studied. AG shows no obvious cytotoxicity within the range of working concentration (1–64 μg/ml) and it exerts potent anti-inflammatory effect independent on Dectin-1 and TLR2. AG/pDNA nanocomposites prepared by electrostatic interaction possess an appropriate particle size ranged from 192.8 to 118.4 nm and zeta potentials ranged from 20.880 to 27.16 mV with the N/P ratios from 5 to 100. AG/pDNA nanocomposites at the N/P ratios of 10 and 20 were able to show superior transfection efficiencies in RAW 264.7 cells as a result of their suitable particle size, zeta potential, anti-inflammatory effect, and the specific interaction with pattern recognition receptors (Dectin-1 and TLR2). These results indicate that AG is a potential candidate for DNA delivery system due to its potent anti-inflammatory effect and high transfection efficiency.
研究领域:
药学
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生物技术
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免疫学
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分子生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
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IF 8.5
Yu Zhang,Zhihong Zhou,Zeming Zhang,Yan Liu,Wenting Ji,Jinglin Wang,Kaiping Wang,Qiang Li
Ulcerative colitis (UC) involves chronic, complex pathology of the intestinal mucosa. Current treatments are limited in efficacy and associated with adverse effects, highlighting the urgent need for improved therapeutic options. Lentinan (LNT), a polysaccharide drug commonly used in clinical immune modulation therapies, shows potential for UC treatment, though its specific targets and mechanisms remain unclear. In this study, LNT administration effectively mitigated DSS-induced colitis in mice, enhanced mucosal barrier function and antimicrobial defense. Specifically, LNT modulated the balance between tissue-resident and infiltrating macrophages, thereby improving pathogen clearance and enhancing the immunological barrier. Notably, we identified a novel effect of LNT in regulating the macrophage Dectin-1-ILC3 axis to increase IL-22 secretion. This led to the modulation of epithelial O-glycan fucosylation, antimicrobial peptides, and epithelial stem cells, thereby strengthening antimicrobial defenses and the physicochemical barrier. Neutralization with anti-IL-22 antibodies diminished the therapeutic effect of LNT in UC, underscoring the critical role of IL-22 in LNT-mediated treatment. Overall, this study highlights the potential of LNT as a novel therapeutic agent for UC, offering new insights into its molecular mechanisms and clinical application.
研究领域:
免疫学
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胃肠病学
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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
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