INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Wen-Jing Xiao,Su Dong,Yue Xuan,Xiao-Jie Huang,Jing-Rui Feng,Hong-Jing You,Yang Chen
Existing studies lack systematic investigation of the polysaccharide components in Citri Reticulatae Pericarpium (CRP), despite established anti-inflammatory and cardioprotective effects of its bioactive constituents. This study isolated and characterized CRP-derived polysaccharides, focusing on CP-0's protective role against Lactobacillus casei cell wall extract (LCWE)-induced endothelial barrier dysfunction. Structural characterization identified CP-0 and CP-1 as novel triple-helical heteropolysaccharides (MW 81,404 and 83,540 Da; glucose, ribose, mannose). Following isolation and physicochemical screening, CP-0 exhibited low cytotoxicity and high anti-inflammatory activity. Mechanistic analyses revealed that CP-0 attenuated LCWE-induced endothelial injury by reducing inflammatory infiltration, IL-1β levels, and adhesion molecules (VCAM-1/ICAM-1) while upregulating tight junction proteins ZO-1/2 in mouse microvascular endothelial cells (MVECs). CP-0 suppressed NLRP3 inflammasome activation via decreased colocalization of NLRP3/Caspase-1/ASC, and competitive binding assays confirmed its interaction with TLR2, which blocked NF-κB nuclear translocation. By targeting TLR2-mediated signaling pathways, CP-0 effectively mitigated LCWE-induced coronary arteritis in vitro, demonstrating potential as a therapeutic candidate for cardiovascular diseases through early-stage anti-inflammatory intervention.
研究领域:
生药学
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免疫药理学
·
血管生物学
·
天然产物化学
·
炎症研究
✓ 已验证
DOI
PubMed
高影响因子
Cell Reports
·
2021
·
IF 9.423
Congwei Han,Jinji Song,Junqing Hu,Huijie Fu,Yanxian Feng,Ruoyu Mu,Zhen Xing,Zhenzhen Wang,Lintao Wang,Junfeng Zhang,Chunming Wang,Lei Dong
Summary Administration of probiotics to regulate the immune system is a potential anti-tumor strategy. However, oral administration of probiotics is ineffective because of the poor inhabitation of exogenous bacteria in host intestines. Here we report that smectite, a type of mineral clay and established anti-diarrhea drug, promotes expansion of probiotics (especially Lactobacillus ) in the murine gut and subsequently elicits anti-tumor immune responses. The ion-exchangeable microstructure of smectite preferentially promotes lactic acid bacteria (LABs) to form biofilms on smectite in vitro and in vivo . In mouse models, smectite laden with LAB biofilms ( Lactobacillus and Bifidobacterium ) inhibits tumor growth (when used alone) and enhances the efficacy of chemotherapy or immunotherapy (when used in combination with either of them) by activating dendritic cells (DCs) via Toll-like receptor 2 (TLR2) signaling. Our findings suggest oral administration of smectite as a promising strategy to enrich probiotics in vivo for cancer immunotherapy.
研究领域:
肿瘤学
·
免疫学
·
微生物学
·
药理学
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DOI
PubMed
高影响因子
MOLECULAR IMMUNOLOGY
·
2018
·
IF 3.188
Gang Chi,Xin-Xia Feng,Ying-Xia Ru,Ting Xiong,Yuan Gao,Han Wang,Zhen-Long Luo,Ran Mo,Fang Guo,Yong-Pei He,Gui-Mei Zhang,De-An Tian,Zuo-Hua Feng
Autoimmune hepatitis (AIH), a serious autoimmune liver disease, can be a lifelong illness, leading to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). So far the mechanisms for disease initiation are largely unknown. Here we report that the amplified non-AIH liver inflammation could promote the initiation of AIH due to the sustained increase of IL-6, IL-12, IL-4, and IL-25 in the liver. The liver injury resulting from virus (adenovirus) or chemicals (CCl 4 ) could induce an amplified (stronger/long-lasting) hepatic inflammation by releasing the ligands for TLR2/TLR4. The amplified inflammation resulted in the increase of multiple cytokines and chemokines in the liver. Among them, the sustained increase of IL-6/IL-12 resulted in the activation of STAT3 and STAT4 in hepatic CD4 + CD25 + Treg cells, thus suppressing Foxp3 gene expression to reduce the suppressive function of Treg cells in the liver, but not those in the spleen. The increase of IL-12 and the impairment of Treg function promoted Th1 response in presence of self-mimicking antigen (human CYP2D6). Intriguingly, the amplified inflammation resulted in the increase of IL-4 and IL-25 in the liver. The moderate increase of IL-4 was sufficient for cooperating with IL-25 to initiate Th2 response, but inefficient in suppressing Th1 response, favoring the initiation of autoimmune response. Consequently, either adenovirus/CYP2D6 or CCl 4 /CYP2D6 could induce the autoimmune response and AIH in the mice, leading to hepatic fibrosis. The findings in this study suggest that the amplified non-AIH inflammation in the liver could be a driving force for the initiation of autoimmune response and AIH.
研究领域:
免疫学
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肝病学
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自身免疫疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2024
·
IF 10.8
Qing Xia,Yuan Wei,Long-ji Hu,Fan-mei Zeng,Yu-wei Chen,Dan Xu,Yuan Sun,Lu-wei Zhao,Yi-fei Li,Guan-hua Pang,Wen Peng,Miao He
Previous studies have detected microplastics (MPs) in human biological samples, such as lungs, alveolar lavage fluid, and thrombus. However, whether MPs induce health effects after inhalation are unclear. In this study, fluorescent polystyrene microplastics (PS-MPs) were found in the thymus, spleen, testes, liver, kidneys, and brain on day 1 or day 3 after one intratracheal instillation. Furthermore, mice showed inflammation in multiple organs, manifested as obvious infiltration of neutrophils and macrophages, increased Toll-like receptors (TLRs), myeloid differentiation primary response protein 88 (MyD88) and nuclear factor-κB (NF-κB), as well as proinflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1β) in the lungs, thymus, spleen, liver, and kidneys after four intratracheal instillations of PS-MPs at once every 2 weeks. Hepatic and renal function indexes were also increased. Subsequently, the inflammatory response in multiple murine organs was significantly alleviated by TLR2 and TLR4 inhibitors. Unexpectedly, we did not find any elevated secretion of monocyte chemotactic protein (MCP)-1 or TNF-α by RAW264.7 macrophages in vitro. Thus, PS-MPs induced inflammatory injuries in multiple murine organs via the TLRs/MyD88/NF-κB pathway in vivo, but not macrophages in vitro. These results may provide theoretical support for healthy protection against PS-MPs and their environmental risk assessment.
研究领域:
环境科学
·
免疫学
·
毒理学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Min Li,Jia-Yao Si,Peng-Fei Xie,Zhen-Jie Feng,Sheng-Jie Li,Feng Zhou,Jian-Mei Li
The global aging crisis has increased the risk of atherosclerosis (AS), positioning vascular senescence as a critical therapeutic target. Procyanidin C1 (PCC1), a bioactive polyphenol from hawthorn, demonstrates dual senolytic and longevity-enhancing effects. This study explored the regulatory role and mechanisms of PCC1 in AS using an ApoE −/− mouse model fed a high-fat diet (HFD) and a D-galactose (D-Gal)-induced cellular senescence model. Hawthorn oligomeric proanthocyanidins (HOPCs), as well as PCC1, showed potent anti-atherosclerotic and anti-aging effects by improving serum lipid metabolism and reducing aortic root plaque, vascular senescence markers and inflammatory adhesion molecules. Metabolomic analysis demonstrated that PCC1 significantly suppresses key enzymes in arachidonic acid (AA) metabolism, thereby decreasing downstream pro-inflammatory mediators. Target identification studies, including drug affinity responsive target stability (DARTS) assay, liquid chromatography-tandem mass spectrometry (LC-MS/MS), cellular thermal shift assay (CETSA), and molecular docking, identified heat shock protein 90 (HSP90) as a direct target of PCC1, leading to inhibition of its downstream signaling. In vitro, PCC1 selectively cleared senescent cells, suppressed the senescence-associated secretory phenotype (SASP), enhanced endothelial nitric oxide synthase (eNOS) phosphorylation, and inhibited the toll-like receptor 2 (TLR2)/nuclear factor kappa-B (NF-κB) pathway, demonstrating multimodal anti-aging and anti-inflammatory effects. Together, these findings indicate that PCC1 mitigates atherosclerosis by targeting both metabolic and inflammatory pathways through senescent cell clearance and HSP90-mediated blockade of the TLR2/NF-κB signaling axis. This dual mechanism highlights PCC1 as a promising vasoprotective agent and supports the potential application of hawthorn extracts in functional foods aimed at preventing aging-related cardiovascular diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2022
·Vol. 9
·期 34
·2203236
·
IF 17.521
Zhencheng Liao,Yiming Niu,Zhenzhen Wang,Jiaxi Chen,Xiaoyan Sun,Lei Dong,Chunming Wang
3D printing enables the customized design of implant structures for accurately regulating host responses. However, polysaccharides, as a major biomaterial category with versatile immune activities, are typically “non-printable” due to the collapse of their filaments extruded during printing. This challenge renders their potential as immunomodulatory scaffolds underexploited. Here, inspired by the quench hardening in metal processing, a nonsolvent quenching (NSQ) strategy is innovatively designed for the 3D printing of polysaccharides. Through rapid solvent exchanging, NSQ instantly induces surface hardening to strengthen the polysaccharide filaments upon extrusion, requiring neither chemical modification nor physical blending that alters the material properties. Tested with five polysaccharides with varying physicochemical properties, NSQ prints predesigned structures at organ-relevant scales and a long shelf-life over 3 months. Glucomannan scaffolds, fabricated via NSQ with different grid spacings (1.5 and 2.5 cm), induce distinct host responses upon murine subcutaneous implantation—from specific carbohydrate receptor activation to differential immunocytes accumulation and tissue matrix remodeling—as mechanistically validated in wild-type and Tlr2 −/− knockout mice. Overall, NSQ as a facile and generic strategy is demonstrated to fabricate polysaccharide scaffolds with improved shape fidelity, thereby potentially unmasking their accurate immunomodulatory activities for future biomaterials design.
研究领域:
生物材料工程
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免疫学
·
组织工程
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
·
2024
·
IF 10.3
Jinping Fan,Yuhan Zhang,Minyu Zuo,Shixuan Ding,Jingjing Li,Shengkai Feng,Yingping Xiao,Shiyu Tao
Deoxynivalenol (DON) is a common environmental pollutant that poses a serious health risk to humans worldwide. This study was aim to explore whether gut microbiota is involved in DON-induced intestinal toxicity as well as to reveal effect of probiotics derived from gut microbiota in protecting intestinal barrier and to elucidate mechanism. We found that DON caused disturbed gut microbiota, particularly Lactobacillus murinus ( L. murinus ) deficiency. DON enhanced M1 macrophage polarization and decreased tight junction protein expression. Microbiota transplantation experiments showed that transfer of DON-disrupted microbiota to healthy mice resulted in delivery of DON-induced intestinal toxicity. Besides, DON lost its damaging effect on macrophage and intestinal barrier in antibiotic-treated mice. Further intervention experiments revealed that L. murinus induce macrophage conversion from M1 to M2 phenotype through secreted extracellular vesicles (EVs) to alleviate DON-induced intestinal barrier disruption. Mechanistically, EVs activate TLR2 to promote M2 macrophage polarization and release IL-10, which in turn enhances intestinal barrier function. Upon successful translation of its efficacy into clinical practice, EVs created from L. murinus could be a novel possible treatment strategy for DON-induced gut disease.
研究领域:
微生物学
·
免疫学
·
胃肠病学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Lang Chen,Chenyan Yu,Wanting Xu,Yuan Xiong,Peng Cheng,Ze Lin,Zhenhe Zhang,Leonard Knoedler,Adriana C. Panayi,Samuel Knoedler,Junqing Wang,Bobin Mi,Guohui Liu
Ongoing research has highlighted the significance of the cross-play of macrophages and mesenchymal stem cells (MSCs). Lysine-specific demethylase 6B (KDM6B) has been shown to control osteogenic differentiation of MSCs by depleting trimethylated histone 3 lysine 27 (H3K27me3). However, to date, the role of KDM6B in bone marrow-derived macrophages (BMDMs) remains controversial. Here, a chromatin immunoprecipitation assay (ChIP) proved that KDM6B derived from osteogenic-induced BMSCs could bind to the promoter region of BMDMs’ brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1) gene in a coculture system and activate BMAL1. Transcriptome sequencing and experiments in vitro showed that the overexpression of BMAL1 in BMDM could inhibit the TLR2/NF-κB signaling pathway, reduce pyroptosis, and decrease the M1/M2 ratio, thereby promoting osteogenic differentiation of BMSCs. Furthermore, bone and macrophage dual-targeted GSK-J4 (KDM6B inhibitor)-loaded nanodiscs were synthesized via binding SDSSD-apoA-1 peptide analogs (APA) peptide, which indirectly proved the critical role of KDM6B in osteogenesis in vivo. Overall, we demonstrated that KDM6B serves as a positive circulation trigger during osteogenic differentiation by decreasing the ratio of M1/M2 both in vitro and in vivo. Collectively, these results provide insight into basic research in the field of osteoporosis and bone repair.
研究领域:
干细胞生物学
·
免疫学
·
骨生物学
·
分子生物学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Chen Zhang,Zhao Zhao,Yi-Jun Jia,Peng-Qi Zhang,Yun Sun,Yong-Can Zhou,Gao-Xue Wang,Bin Zhu
Viral diseases have constantly caused great threats to global public health, resulting in an urgent need for effective vaccines. However, the current viral vaccines often show low immunogenicity. To counter this, we report a smart strategy of a well-designed modular nanoparticle (LSG-TDH) that recapitulates the dominant antigen SG, low-molecular-weight protamine, and tetralysine-modified H-chain apoferritin (TDH). The constructed LSG-TDH nanovaccine could self-assemble into a nanocage structure, which confers excellent mucus-penetrating, cellular affinity, and uptake ability. Studies demonstrate that the LSG-TDH nanovaccine could strongly activate both mucosal and systemic immune responses. Importantly, by immunizing wild-type and TLR2 knockout (TLR2-KO) zebrafish, we found that TLR2 could mediate LSG-TDH-induced adaptive mucosal and systemic immune responses by activating antigen-presenting cells. Collectively, our findings offer new insights into rational viral vaccine design and provide additional evidence of the vital role of TLR2 in regulating adaptive immunity.
研究领域:
病毒学
·
免疫学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Nian-Yuan Xu,Jun Li,Mei-Ling Wang,Xue-Yu Chen,Ruizhi Tang,Xi-Qiu Liu
The current research models of breast cancer are usually limited in their capacity to recapitulate the tumor microenvironment in vitro. The lack of an extracellular matrix (ECM) oversimplifies cell–cell or cell–ECM cross-talks. Moreover, the lack of tumor-associated macrophages (TAMs), that can comprise up to 50% of some solid neoplasms, poses a major problem for recognizing various hallmarks of cancer. To address these concerns, a type of direct breast cancer cells (BCCs)–TAMs coculture organoid model was well developed by a sequential culture method in this study. Alginate cryogels were fabricated with appropriate physical and mechanical properties to serve as an alternative ECM. Then, our previous experience was leveraged to polarize TAMs inside of the cryogels for creating an in vitro immune microenvironment. The direct coculture significantly enhanced BCCs organoid growth and cancer aggressive phenotypes, including the stemness, migration, ECM remodeling, and cytokine secretion. Furthermore, transcriptomic analysis and protein–protein interaction networks implied certain pathways (PI3K-Akt pathway, MAPK signaling pathway, etc.) and targets (TNF, PPARG, TLR2, etc.) during breast cancer progression in a TAM-leading immune microenvironment. Future studies to advance treatment strategies for BCC patients may benefit from using this facile model to reveal and target the interactions between cancer signaling and the immune microenvironment.
研究领域:
肿瘤学
·
生物医学工程
·
细胞生物学
·
免疫学
·
组织工程
✓ 已验证
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2024
·
IF 3.3
Miao Yang,Kanmin Mao,Xin Cao,Hongjuan Liu,Weifeng Mao,Liping Hao
Benzo[ a ]pyrene (BaP) is a ubiquitous environmental pollutant posing various toxicity effects on organisms. Previous studies demonstrated that BaP could induce hepatotoxicity, while the underlying mechanism remains incompletely elucidated. In this study, a comprehensive strategy including network toxicology, transcriptomics and gut microbiomics was applied to investigate the hepatotoxicity and the associated mechanism of BaP exposure in mice. The results showed that BaP induced liver damage, liver oxidative stress and hepatic lipid metabolism disorder. Mechanistically, BaP may disrupt hepatic lipid metabolism through increasing the uptake of free fatty acid (FFA), promoting the synthesis of FA and triglyceride (TG) in the liver and suppressing lipid synthesis in white adipose tissue. Moreover, integrated network toxicology and hepatic transcriptomics revealed that BaP induced hepatotoxicity by acting on several core targets, such as signal transducer and activator of transcription 1 (STAT1), C-X-C motif chemokine ligand 10 (CXCL10) and toll-like receptor 2 (TLR2). Further analysis suggested that BaP inhibited JAK2-STAT3 signaling pathway, as supported by molecular docking and western blot. The 16S rRNA sequencing showed that BaP changed the composition of gut microbiota which may link to the hepatotoxicity based on the correlation analysis. Taken together, this study demonstrated that BaP caused liver injury, hepatic lipid metabolism disorder and gut microbiota dysbiosis, providing novel insights into the hepatotoxic mechanism induced by BaP exposure.
研究领域:
毒理学
·
分子生物学
·
基因组学
·
微生物组学
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产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2025
·
IF 2.6
Shengjie Wang,Wei Liu,Chao Yang,Changwei Li,Xianlong Zhang
Implant-associated infections (IAI) present a significant clinical challenge. Effective prevention of and recovery from IAI is complex, involving antibacterial treatment and the promotion of bone integration. However, the current artificial implants used in clinics often lack effective antibacterial properties and have limited functionality. In this study, Lipopeptide 01 (LP01), a lipopeptide derived from the skin commensal Staphylococcus epidermidis is successfully immobilized, onto the porous surface of sulfonated Poly (ether-ether-ketone) (SPEEK) to create a novel artificial implant, LP01-PS. Both in vivo and in vitro experiments demonstrates that LP01-PS displays favorable material properties, biocompatibility, outstanding antibacterial characteristics, and the ability to promote bone formation. Mechanistically, LP01-PS enhances antibacterial activities by triggering TLR2/P65 signaling, upregulating the expression of LL37 and β-defensins in macrophages. Furthermore, it can boost the osteogenic differentiation capability of bone marrow mesenchymal stem cells (BMSCs) through the β-catenin signaling pathway, thereby facilitating bone formation. The discovery of LP01-PS with dual antibacterial and osteogenic effects, coupled with insights into its mode of action, suggests that LP01-PS can serve as a promising implant material to enhance the success rates of total joint replacement surgeries, mitigate the risks of infection and prosthetic loosening, and foster the repair and regeneration of bone tissue.
研究领域:
生物医学工程
·
材料科学
·
免疫学
·
再生医学
·
骨科
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）