Molecular Medicine Reports
·
2019
·Vol. 19
·期 5
·3707-3713
·
IF 1.851
Shuyu Liang,Jinzhen Cai,Yani Li,Rui Yang
Macrophage polarization serves an important role in immune regulation that is regulated by T‑cell immunoglobulin‑mucin‑3 (Tim‑3). The objective of the present study was to explore the role of 1,25‑dihydroxy‑vitamin D3 [1,25(OH)2D3] in macrophage polarization. Plasmid transfection techniques were applied to prepare RAW264.7 cells with silenced or overexpressed Tim‑3 gene. ELISAs were used to examine the level of inflammatory factors secreted by macrophages. Proteins levels were determined by western blot analysis. mRNAs expression levels were assessed using reverse transcription quantitative polymerase chain reaction. It was identified that 1,25(OH)2D3 upregulated Tim‑3 levels and promoted the secretion of interleukin (IL)‑10. 1,25(OH)2D3 was also observed to increase the level of transforming growth factor‑β and to inhibit tumor necrosis factor‑α and IL‑6. The results also suggested that Tim‑3 gene silencing induced macrophages polarization to classically activated macrophages (M1), and that overexpression of the Tim‑3 gene induced macrophage polarization to alternatively activated macrophages (M2). 1,25(OH)2D3 treatment upregulated the expression level of Tim‑3 in macrophages, which promoted cell polarization to M2 and inhibited polarization to M1. The data from the present study indicated that Tim‑3 may induce macrophage polarization to M2, and that 1,25(OH)2D3 produced immunosuppressive effects by upregulating Tim‑3.
研究领域:
免疫学
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细胞生物学
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药理学
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PubMed
高影响因子
Journal of Functional Foods
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2025
·
IF 4
Lifang Feng,Tianyu Zhang,Wei Ye,Daofeng Qu
Resveratrol and rutin, two polyphenolic compounds, can effectively alleviate the symptoms of ulcerative colitis (UC), leading to conflicts in recommending resveratrol- or rutin-rich diets to UC patients, who do not know which type of diet is more effective in alleviating UC symptoms. In this study, administration of resveratrol or rutin alleviated DSS-induced UC mice, including reduction of DAI, serum levels of inflammatory cytokines and oxidant, and improvement of colonic health status. Differentially expressed genes resulting from resveratrol and rutin treatment in DSS-induced UC mice at the genome-wide level from scratch and elucidated the mechanism by which they affected the polarization of intestinal epithelial T cells by promoting Treg cells and inhibiting Th17 cells to alleviate UC symptoms, and rutin was greater than resveratrol. In addition, rutin-rich foods were superior to resveratrol-rich foods in ameliorating UC symptoms in mice. Our findings suggest that UC patients consume rutin-rich foods to better alleviate intestinal inflammation.
研究领域:
免疫学
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胃肠病学
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营养生物化学
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分子生物学
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Science Immunology
·
2026
·Vol. 11
·期 121
·
IF 16.4
Weiwei Yu,Ruya Sun,Xiaoyang Lu,Qiqi Deng,Heng Zhang,Sheng Chen,Siqi Dai,Tianyi Hu,Xiangyuan Li,Yidong Yang,Lihao Chen,Zhexu Chi,Jian Zhang,Siwen Zhang,Yiyi Zhu,Dehang Yang,Qianzhou Yu,Zhen Wang,Quanquan Wang,Fan Yang,Qian Xiao,Kefeng Ding,Di Wang
Tumor cells promote metabolic dysregulation of immune cells by controlling the metabolic landscape of the tumor microenvironment. It is unclear whether tumors restrict specific nutrients to drive rapid growth and immune evasion in addition to the overconsumption of nutrients to support anabolism. We identified that up-regulation of solute carrier family 7 member 1 (SLC7A1) increased arginine utilization and promoted tumor growth, whereas down-regulation of SLC7A2 decreased lysine catabolism to support immune evasion. Repression of lysine catabolism in tumor cells reduced glutaconic acid (GC), a medium-chain acyl-CoA dehydrogenase–dependent lysine catabolite that has immunostimulatory effects on antitumor CD8 T cells. GC modified pyruvate kinase M2 (PKM2) through posttranslational glutaconylation at key lysine residues Lys 336 (K336) and K337. This modification reinforced PKM2 dimers, transcriptionally driving metabolic reprogramming and reinvigorating antitumor CD8 T cells. Our study highlights an amino acid trade-off that dynamically optimizes the metabolic preferences of tumors to promote proliferation and immune evasion.
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EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Ying Huang,Jiale Li,Yingzhou Qin,Bo Qie,Qianqian Wang,Cuijuan Liu,Yimin Zhu
A cyclic peptide binding with TIM-3, TBP1, was screened by a novel CX 12 C cyclic peptide display library base on bacterial surface display. • TBP1 effectively disrupted TIM-3 interactions with CEACAM-1 and PtdSer. • TBP1 restored the function of exhausted T cells in vitro . • TBP1 synergized with anti-PD-1 antibody, improving anti-tumor immunity in vivo . Immune checkpoint blockade (ICB) therapies, particularly antibodies blocking, the programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1), have shown clinical success but remain limited by suboptimal response rates, often due to insufficient immune activation. T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3), a non-redundant immune checkpoint frequently co-expressed with PD-1, drives severe T-cell exhaustion in solid tumors and contributes to resistance against anti-PD-1/PD-L1 therapy. Thus, dual blockade of TIM-3 and PD-1 may restore more effective anti-tumor immunity. Compared to antibodies, low-molecular-weight peptides offer advantages in combination therapy, including better tissue penetration, lower immunogenicity, improved tolerability and low production costs. Cyclic peptides, in particular, provide enhanced biological activity and proteolytic stability. Here, we present TBP1, a cyclic peptide identified via a bacterial surface display library, which binds TIM-3 with high affinity and specificity. Competitive blocking assays and molecular docking confirmed that TBP1 effectively disrupts TIM-3 interactions with Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) and Phosphatidylserine (PtdSer). In vitro , TBP1 restored exhausted T-cell function by disrupting the TIM-3/CEACAM-1 interaction. In CT26 tumor-bearing mice, TBP1 synergized with an anti-PD-1 antibody, enhancing anti-tumor immunity by promoting CD4 + T cell infiltration and IL-2 secretion. These findings identify TBP1 as a novel TIM-3-targeting cyclic peptide and support its potential application in combination immune checkpoint blockade. Download: Download high-res image (372KB) Download: Download full-size image
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JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY
·
2025
·
IF 6
Hengyang Liu,Wanyuan Li,Yong Xu,Enzhu Hu,Guangchao Qin,Kunhong Hu
A 1 T/2H-MoS 2 (THM) lubricant additive was synthesized via a solvothermal method to improve the lubrication of poly-alpha-olefin (PAO) and reduce the negative influence of diesel carbon soot (CS). The THM was then modified with Cu to further enhance the wear resistance. The average interlayer spacing of MoS 2 in THM and the Cu-modified THM (CTHM) was 0.99 nm, significantly larger than the 0.63 nm of 2H-MoS 2 nanoparticles. In PAO, CTHM demonstrated a 45 % improvement in friction reduction and a 77 % increase in wear resistance compared to 2H-MoS 2 . While the friction reduction of CTHM was similar to that of THM, CTHM exhibited 36 % superior wear resistance. In CS-contaminated PAO, CTHM outperformed 2H-MoS 2 with a 37 % reduction in friction and a 29 % enhancement in wear resistance. The Cu modification reduced the oxidation of CTHM and the conversion of 1 T-MoS 2 to 2H-MoS 2 in the tribofilm, contributing to improved wear resistance. The CS contamination negatively influenced the lubrication by accelerating MoS 2 oxidation, catalyzing the transition from 1 T-MoS 2 to 2H-MoS 2 , and inhibiting Cu incorporation into the tribofilm. Nonetheless, the effect of CS on CTHM and THM was less severe than on 2H-MoS 2 . This work provides an alternative method to alleviated the antagonism between MoS 2 and CS.
研究领域:
材料科学
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润滑工程
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JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Nan Li,Weiwei Mu,Zhenxing Xia,Qingping Ma,Ruihua Feng,Panpan Gu,Qinglin Yang,Shuying Gao,Weihan Zhang,Suyun Wei,Yi Zheng,Wei Zhao,Yongjun Liu,Na Zhang
Therapeutic tumor vaccines, which activate self-T cells to eliminate tumors, hold tremendous promise in future cancer immunotherapy with high specificity and low side effects. To effectively activate T cell, dendritic cells (DCs) need simultaneously provide three indispensable signals to naive T cells, including MHC-antigen signal, costimulation signal and cytokine stimulation. However, current marketed therapeutic tumor vaccines still suffer from lacking the ability to activate three stimulation signals at the same time, which resulted to the low response rate and unsatisfied therapeutic efficiency. Here, we proposed a soluble microneedle-based tumor vaccines (TR-12@LGMN) which facilitate triple activation of antigen presentation and induce high immune response rate. First, the melanoma-specific antigen tyrosinaserelated protein-2 (Trp2), Resiquimod (R848), and IL-12 mRNA co-loaded liposomes (TR-12@LIPO) was prepared. The TR-12@LIPO ensured triple-activating three essential signals of antigen presentation through enhancing the binding of MHC I-antigen peptides to T cell receptor (TCR), the binding of CD80/86 on DCs to CD28 on T cells, and the release of cytokines for T cells activation. Second, TR-12@LIPO was co -dispersed in polyvinylpyrrolidone-polyvinyl alcohol (PVP-PVA) matrix with granulocyte-macrophage colony stimulating factor (GM-CSF) to prepare TR-12@LGMN by mold method. The TR-12@LGMN was quadrilateral shape with sufficient mechanical strength for skin piercing. After skin insertion, TR-12@LGMN dissolved in the skin interstitial fluid to release GM-CSF and TR-12@LIPO. DCs were recruited by GM-CSF and uptaked TR-12@LIPO. TR-12@LIPO showed enhancement of cross-presentation by antigen cytoplasmic delivery, DCs maturation and IL-12 secretion. In vivo results showed that TR-12@LGMN could efficiently activate CD8 + T cells, induce antigen-specific cytotoxic T cells (CTLs) and memory T cell (T m ). Ultimately, strong anti-tumor immunity and long-term durable tumor control were achieved in the B16F10 tumor prevention and treatment model. Overall, our work proposes a triple-activated antigen presentation strategy and designs a microneedle-based tumor vaccine for skin delivery, revealing a potential promising direction for the development of new therapeutic tumor vaccines methods.
研究领域:
肿瘤免疫学
·
生物医学工程
·
药剂学
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DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Lihua Yao,He Yang,Fangjian Shan,Xiaomeng Niu,Yichen Wang,Hengyuan Zhang,Sujian Wang,Gaojian Chen,Hong Chen
Gene-engineered T cell therapies, particularly chimeric antigen receptor (CAR)-T cells, have demonstrated remarkable clinical success. However, concerns regarding insertional mutagenesis and other risks associated with genetic modification remain. Here, a non-genetic strategy is presented for T cell engineering using glycopolymer modification. It develops glycopolymer-modified T (G-T) cells based on antigen-specific T cells by integrating metabolic glycoengineering and click chemistry, yielding cells that retain T cell functionality while significantly enhancing tumor enrichment. The polyvalent glycopolymer-receptor interactions significantly improved the binding affinity of G-T cells to various glucose transporter 1 (GLUT1)-overexpressing tumor cells, resulting in increased cytotoxicity compared to unmodified T cells. In the tumor microenvironment, G-T cells engaged in stronger immune crosstalk with dendritic cells (DCs), upregulating interferon-gamma (IFN-γ) and interleukin-12 (IL-12) secretion and amplifying the anti-tumor immune response. Notably, despite the lower specificity of glycan–receptor interactions compared to antigen–antibody binding, the findings reveal an unexpected advantage: the “less restrictive” nature of glycan–receptor recognition enhances both tumor and immune cell interactions, triggering a potent immune cascade. This study establishes a universal, non-genetic T cell engineering strategy with broad applicability, offering a new perspective for tumor immunotherapy by merging biomedical polymer materials with immune modulation.
研究领域:
免疫治疗
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生物工程
·
糖生物学
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肿瘤免疫学
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高分子科学
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分子医学
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DOI
PubMed
高影响因子
Science Immunology
·
2025
·Vol. 10
·期 108
·
IF 16.3
Limin Cao,Li Wang,Zhihong Li,Xia Wei,Jinqiu Ding,Chun Zhou,Xia Chen,Zhicheng Huang,Zhugui Shao,Junchen Shen,Hongfei Lou,Keqing Zhao,Yuwei Huang,Yuanqin Yang,Han Liu,Yumeng Sun,Junling Niu,Shan Jiang,Rong Lu,Longhai Tang,Xiaoming Zhang,Haibing Zhang,Yichuan Xiao,Jianfeng Chen,Shixin Ma,Chengjiang Gao,Guangxun Meng,Li Liu,Zhaozhu Qiu,Haopeng Wang,Liufu Deng,Youqiong Ye,Xin-Ming Jia,Huabin Li,Hui Xiao
The volume-regulated anion channels (VRACs) transport osmolytes, neurotransmitters, and cyclic GMP-AMP (cGAMP) across the cell membrane to regulate cell volume and host defense. We report that the leucine-rich repeat–containing 8A/C (LRRC8A/C) VRAC plays a crucial role in immune responses to radiotherapy and chemotherapy for cancer. VRACs transfer cGAMP from irradiated cancer cells to infiltrating CD4 and CD8 T cells, thus enhancing their effector functions. TCR signaling acts as a physiological signal to open the VRAC pore through phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] and reactive oxygen species (ROS). This allows the rapid uptake of cGAMP and STING activation in mouse and human T cells and induction of interferon-α/β, which up-regulate granzymes and IFN-γ in CD8 T cells. Inhibition of the extracellular hydroxylases CD39 and ENPP1 maintains extracellular ATP and cGAMP, which promotes VRAC-enhanced CD8 T cell anticancer function. Thus, the transfer of cGAMP to T cells by VRACs may be a strategy that can be targeted in future cancer therapies.
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JOURNAL OF ALLOYS AND COMPOUNDS
·
2022
·
IF 6.371
Wei Shen,Liang Qiao,Juan Ding,Yongming Sui
Tailoring tantalum disulfide (TaS 2 ) electrocatalysts with tunable stacking architecture and phase structure is of great importance for advancement of hydrogen evolution reaction (HER). In this work, stacking architecture- and phase- modulated tantalum disulfide nanosheets are reported through a facile liquid phase synthesis strategy. Accordion-like nanosheets , vertical nanosheets and ultrathin nanosheets are named according to their obvious stacking architecture, and 1 T-2 H mixed phase structures containing different degrees of 2 H phases are realized. High-resolution transmission electron microscopy shows that there are obvious lattice defects in the nanosheets. Tantalum disulfide nanosheets synergistically integrate multiple advantages of nanostructure engineering, phase engineering and defect engineering. In the HER process, the ultrathin tantalum disulfide nanosheet structure is conducive to the in-plane electron transfer , and its close contact with the electrode surface makes the charge transfer faster and has the best HER activity. The overpotential of the ultrathin nanosheet electrocatalyst at 10 mA cm −2 is 280 mV. After 10,000 CV cycles and over 40 h of i-t test, the catalyst still has high stability in acidic media. Theoretical calculations show that the addition of 2 H phase structure and rich defects improves the intrinsic activity and active sites, and jointly promotes the improvement of HER performance. Our work integrates a variety of optimal regulation methods into TaS 2 nanosheets, providing a new idea for the construction of advanced electrocatalysts for water electrolysis.
研究领域:
材料科学
·
电催化
·
纳米材料
·
能量转换
·
计算化学
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DOI
高影响因子
Food Bioscience
·
2026
·
IF 5.9
Kai Cheng,Gang Wang,Jianhua Xie,Zhibing Huang
Penicillium polysaccharides exhibit immunomodulatory activity, different polysaccharides produced by Penicillium EF-2 during fermentation were altered by adding different concentrations of genistein as an exogenous additive to change the fermentation environment. Structural characterization of the polysaccharides was performed and their activities were evaluated, and it was found that the Penicillium polysaccharides became more porous and their molecular weight decreased after the addition of genistein, thereby increasing their biological activity. Combined cell-based and animal studies demonstrated that genistein addition enhances the bioactivity of extracellular polysaccharides produced by Penicillium fermentation. However, for polysaccharide yield in Penicillium fermentation, polysaccharide content decreased at 3 d in both 0.5 g/L genistein (G_0.5E) and 1.5 g/L genistein (G_1.5E) treatments. Furthermore, it was concluded that polysaccharides may influence T cell differentiation by regulating energy metabolism, thereby exerting an immunosuppressive regulatory effect.
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Advanced Science
·
2025
·
IF 14.1
Hongyan Yu,Jingxu Zhang,Qingping Liu,Duxing Li,Ruonan Pan,Gan Miao,Yidi Chen,Zhe Kou,Guangbo Qu,Rong Zhang,Xiaoting Jin,Yuxin Zheng
Volatile organic compounds (VOCs) emitted from interior decorations are suggested to pose substantial respiratory hazards as they disturb the immune response in the lung. Despite this, the characteristics and mechanisms underlying immune cell responses to real-world VOC mixtures, rather than previously individual or dominant VOC species, remain poorly understood. Employing a whole-body inhalation exposure model, we reveal that interior decorative VOCs alter pulmonary immune cell profiles with a persistent increase in alveolar T cells. This sustained elevation results from intensified lymphoid-biased hematopoiesis in the bone marrow (BM) rather than in situ lung, which is followed by thymic maturation and subsequent recruitment to lung tissues. The ex vivo biosensor and antibody neutralization assays clarify that VOCs-induced lymphoid-biased hematopoiesis is primarily driven by osteogenic differentiation within the BM niche, a process further regulated by interleukin-6 (IL-6) and interleukin-17A (IL-17A). Moreover, the cohort study associates VOCs-expanded lymphocytes with increased risks of obstructive lung diseases, where exposed individuals show elevated IL-6 and IL-17A levels, correlating with VOC concentrations and lymphocyte proportions. These findings highlight compelling indicators (i.e., T cells) and potential interventions (i.e., IL-6 and IL-17A) for evaluating and mitigating VOC-associated respiratory risks.
研究领域:
免疫学
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环境健康
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呼吸医学
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毒理学
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造血生物学
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分子生物学
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PubMed
高影响因子
ChemNanoMat
·
2025
·Vol. 11
·期 7
·e202500102
·
IF 2.6
Yuanchao Li,Shixing Han,Pengchao Liang,Xiaokun Shang,Qi Li,Jingjing Ma,Songlin Wang,Li Yang,Guangri Xu
The Na x MnO 2 ( x < 0.44) material with a T-type tunnel phase shows excellent cycling performance, but low initial specific capacity. The Na x MnO 2 ( x > 0.6) with P2-type phase exhibits high initial specific capacity, yet poor cycling performance. Layer-tunnel hybrid materials has served as cathode materials for sodium-ion batteries (SIBs) due to the integration of high specific capacity and superior cycling performance. Herein, sodium manganite composites is synthesized with tunnel phase containing a small amount of P2-type layered phase in Na 0.44 MnO 2 materials using citric acid as the dispersant. The citric acid can promote the transition of the T-P2 phase and contribute to the uniform distribution of elements. The as-prepared Na 0.44 MnO 2 with layered-tunnel hybrid phase exhibits the best overall electrochemical performances with a capacity retention of 68% after 300 cycles at 1 C and an initial discharge capacity of 143.7 mA h g −1 , due to combination of the advantages of layered and tunnel structure. This work provides a new strategy for synthesizing transition metal oxides with hybrid phase as the cathode of advanced SIBs.
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