INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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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
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微生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
International Journal of Biological Sciences
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2024
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IF 8.2
Jianzhi Wu,Liping Gong,Yijie Li,Tiegang Liu,Rong Sun,Kexin Jia,Runping Liu,Fei Dong,Xiaohong Gu,Xiaojiaoyang Li
Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic matrix deposition and irreversible aberrant tissue remodeling. Their mechanisms of action are associated with the activation of macrophages and a disturbed immune environment. We aim to determine how these activated macrophages influenced the pathogenesis of pulmonary fibrosis. We found the fibrotic areas of IPF patients contained more serum and glucocorticoid-induced kinase 1 (SGK1)-positive and M2-type macrophages. Similarly, bleomycin (BLM)+LPS significantly triggered high expression of SGK1 in the IPF mice, accompanied by destroyed lung structure and function, increased fibrosis markers and disturbed immune microenvironment. Mechanistically, SGK1 markedly promoted the reprogramming of M2-type macrophages in fibrotic lungs by triggering glycogen synthase kinase 3beta (GSK3β)-tat-interacting protein 60 (TIP60)- histone-3 lysine-27 acetylation (H3K27ac) signalings, which further released chemokine (C-C motif) ligand 9 (CCL9) to attract Th17 cells and delivered TGF-β to fibroblasts for synergistically destroying immune microenvironment, which was largely reversed by macrophage depletion in mice. We took macrophages as the entry point to deeply analyze IPF pathogenesis and further provided insights for the development of novel drugs represented by SGK1.
研究领域:
肺科学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
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2025
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IF 10.2
Zili Guo,Tao Chen,Xuehuan Wen,Qiangchang Fu,Jiabin Lai,Jiajin Li,Jiayu Chen,Jie Weng,Wang Wen,Qihua Cao,Junxiong Zhu,Zhaoming Ye,Xiaohua Yu,Lifeng Jiang
Osteoarthritis (OA) pathogenesis is profoundly influenced by dysregulated immune dynamics, where persistent interleukin-17 (IL-17)/T helper 17 (Th17) cell mediated inflammation coordinates with failed regenerative processes to perpetuate joint destruction. Here, we unveil the role of myeloid-derived suppressor cells (MDSCs) as dual-phase regulators that paradoxically orchestrate both inflammatory escalation and tissue repair in OA progression. Intra-articular administration of MDSCs in OA mice amplified IL-17 dependent inflammatory cascades and chemokine-driven leukocyte recruitment, revealing a context-dependent pro-inflammatory phenotype. Unexpectedly, MDSC depletion failed to attenuate joint damage, implying their indispensable yet multifaceted role in OA pathogenesis. Mechanistically, MDSCs exhibited functional plasticity by upregulating arginase-1 to polarize M2 macrophages, fostering a regenerative niche alongside their inflammatory activity. To resolve this duality, we developed a bio-responsive hydrogel-microsphere system integrating transforming growth factor β1 (TGF-β1) and interleukin-1 β1 antibody (anti–IL-1β) loaded mesoporous silica nanoparticles (MSNs). This spatiotemporally controlled platform selectively suppressed MDSC-mediated Th17 cell expansion while harnessing their intrinsic capacity to drive M2 macrophage polarization and chondrogenesis. The resultant shift from a pro-inflammatory to pro-regenerative microenvironment significantly attenuated cartilage erosion and restored joint integrity in OA models. Our findings redefine MDSCs as bifunctional immune orchestrators in OA and establish precision biomaterial guided immune decoding as a paradigm-shifting therapeutic strategy. By engineering MDSC plasticity through antagonistic cytokine delivery, this work provides a blueprint for microenvironment remodeling in degenerative joint diseases.
研究领域:
免疫学
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再生医学
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生物材料
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纳米医学
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风湿病学
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2018
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IF 3.909
Song-Tao Fan,Shao-Ping Nie,Xiao-Jun Huang,Sunan Wang,Jie-Lun Hu,Jun-Hua Xie,Qi-Xing Nie,Ming-Yong Xie
In vivo an ecological network of polysaccharides utilization by gut microbiota is not only an intense competition but also an impressive cooperation pattern. The present study evaluated the in vivo protective effect of combined fungal polysaccharides (CFP) from Cordyceps sinensis and Ganoderma atrum on colon immune dysfunction, induced by 150 mg/kg cyclophosphamide (CP). The results showed that C. sinensis polysaccharides (CSP) significantly promoted microbial-derived butyrate to improve histone h3 acetylation mediating regulatory T (Treg) cell specific Foxp3, as well as significantly restored CP-induced elevation of interleukin (IL)-17 and IL-21. Additionally, G. atrum polysaccharides (PSG) significantly down-regulated MyD88, as well as significantly increased IL-10 and TGF-β3. Furthermore, CFP balanced the disequilibrium of cytokines secretion and Foxp3/RORγt ratio related Treg/T helper 17 (Th17) balance, as well as down-regulated the TLR-mediated inflammatory signaling pathway and promoted secretory immunoglobulin A (sIgA) secretion to suppress colonic inflammation. Therefore, our results typically contribute to understand the in vivo immunoregulatory function of fungal polysaccharides compounds, involving microbial-associated inflammatory signals and specific metabolic products.
研究领域:
免疫学
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药理学
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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
SCIENCE OF THE TOTAL ENVIRONMENT
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2019
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IF 5.589
Xia Wang,Jianbo Zhu,Baida Kong,Bingnan He,Lai Wei,Yuanxiang Jin,Yudong Shan,Weitao Wang,Chunqiang Pan,Zhengwei Fu
Short-chain chlorinated paraffins (SCCPs, C 10–13 ) were listed as persistent organic pollutants (POPs) by the Stockholm Convention in 2017 and pose extensive exposure risks to humans. To our knowledge, there have been no studies reporting the immmunomodulatory effects of SCCPs until now. C 9 -CPs have also been shown to be present in the environment. In this study, adult male C57BL/6 mice were exposed to 1, 10, or 100 mg/kg/d C 9–13 -CPs by gavage for 28 d. The results showed that compared to those of the controls, exposure to C 9–13 -CPs led to increased spleen weight, delimited germinal centers, enhanced energy metabolism, and elevated glutathione content, but no variation in the malonaldehyde level in the spleen was observed. Exposure to C 9–13 -CPs also increased the populations of splenic lymphocytes, T lymphocytes, NK cells, and the ratio of the CD3 + /CD19 + subsets and CD4 + /CD8 + subsets compared to those of the controls. RNA-seq revealed 424 differentially expressed genes (DEGs) (fold change ≥ 1.5, FDR < 0.05) in the spleen between the control group and the 100 mg/kg/d C 9–13 -CPs-treated group. KEGG analysis demonstrated that folate biosynthesis, pathways in cancer and thyroid hormone signaling were the three most significantly enriched pathways, and despite not reaching statistical significance, some immune-related pathways were also enriched in the KEGG functional enrichment analysis, including the chemokine signaling pathway (FDR < 0.0584), the NF-κB signaling pathway (FDR < 0.0663), Th17 cell differentiation (FDR < 0.0839), and the Jak-STAT signaling pathway. Moreover, compared to those of the controls, exposure to C 9–13 -CPs enhanced the Concanavalin A (Con A)-stimulated cultured splenocyte proliferation, while the exposure showed no effect on the splenocyte proliferation that was stimulated by lipopolysaccharides (LPS). Taken together, these results demonstrated that subacute exposure to C 9–13 -CPs could have immunomodulatory effects in mice. The present study helps to provide an understanding of the comprehensive health risks posed by C 9–13 -CPs.
研究领域:
毒理学
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免疫学
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分子生物学
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环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子