INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
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2019
·Vol. 44
·期 3
·835-846
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IF 2.928
Bao‑Wen Liu,Zhi‑Xiao Li,Zhi‑Gang He,Qian Wang,Cheng Liu,Xian‑Wei Zhang,Hui Yang,Hong‑Bing Xiang
In this study, we focused on several itch‑related molecules and receptors in the spinal cord with the goal of clarifying the specific mediators that regulate itch sensation. We investigated the involvement of serotonin receptors, opioid receptors, glia cell markers and chemokines (ligands and receptors) in models of acetone/ether/water (AEW)‑ and diphenylcyclopropenone (DCP)‑induced chronic itch. Using reverse transcription‑quantitative polymerase chain reaction, we examined the expression profiles of these mediators in the lower cervical spinal cord (C5‑8) of two models of chronic itch. We found that the gene expression levels of opioid receptor mu 1 (Oprm1), 5‑hydroxytryptamine receptor 1A (Htr1a) and 5‑hydroxytryptamine receptor 6 (Htr6) were upregulated. Among the chemokines, the expression levels of C‑C motif chemokine ligand (Ccl)21, Cxcl3 and Cxcl16 and their receptors, Ccr7, Cxcr2 and Cxcr6, were simultaneously upregulated in the spinal cords of the mice in both models of chronic itch. By contrast, the expression levels of Ccl2, Ccl3, Ccl4 and Ccl22 were downregulated. These findings indicate that multiple mediators, such as chemokines in the spinal cord, are altered and may be central candidates in further research into the mechanisms involved in the development of chronic itch.
研究领域:
神经生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2023
·
IF 7.3
Chen-Yu Jiang,Li-Wei Wu,Yi-Wei Liu,Bei Feng,Lin-Cai Ye,Xu Huang,Yang-Yang He,Yi Shen,Yi-Fan Zhu,Xing-Liang Zhou,Dai-Ji Jiang,Hai-Kun Qi,Hao Zhang,Yi Yan
Objective Inflammation is recognized as a contributor in the development of pulmonary arterial hypertension (PAH), and the recruitment and functional capacity of immune cells are well-orchestrated by chemokines and their receptors. This study is aimed at identification of critical chemokines in the progression of PAH via transcriptomic analysis. Methods Differentially expressed genes (DEGs) from lungs of PAH patients were achieved compared to controls based on Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was applied for functional annotation and pathway enrichement. The abundance of immune cells was estimated by the xCell algorithm. Weighted correlation network analysis (WGCNA) was used to construct a gene expression network, based on which a diagnostic model was generated to determine its accuracy to distinguish PAH from control subjects. Target genes were then validated in lung of hypoxia-induce pulmonary hypertension (PH) mouse model. Results ACKR4 (atypical chemokine receptor 4) was downregulated in PAH lung tissues in multiple datasets. PAH relevant biological functions and pathways were enriched in patients with low-ACKR4 level according to GSEA enrichment analysis. Immuno-infiltration analysis revealed a negative correlation of activated dendritic cells, Th1 and macrophage infiltration with ACKR4 expression. Three gene modules were associated with PAH via WGCNA analysis, and a model for PAH diagnosis was generated using CXCL12, COL18A1 and TSHZ2, all of which correlated with ACKR4. The ACKR4 expression was also downregulated in lung tissues of our experimental PH mice compared to that of controls. Conclusions The reduction of ACKR4 in lung tissues of human PAH based on transcriptomic data is consistent with the alteration observed in our rodent PH. The correlation with immune cell infiltration and functional annotation indicated that ACKR4 might serve as a protective immune checkpoint for PAH.
研究领域:
医学
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免疫学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2024
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IF 4.6
Shengze Zhang,Chuming Luo,Qiqi Chen,Nina Li,Xinzhong Liao,Jiani Wu,Haolu Zha,Ting Xie,Shaohui Bai,Weijian Tian,Lin Zhu,Xuan Zou,Shisong Fang,Caijun Sun,Ying Jiang,Jianhui Yuan,Yuelong Shu,Nan Wu,Huanle Luo
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is crucial in flavivirus infections, modulating the host immune response through interactions with viral proteins. Despite its importance, the relationship between TRAF6 and Zika virus (ZIKV) remains poorly understood. Our prior proteomics analysis revealed reduced TRAF6 protein levels in ZIKV-infected human trophoblast cells compared to non-infected controls. Subsequent studies in cell models and murine tissues confirmed a significant reduction in both TRAF6 mRNA and protein levels post-ZIKV infection. Further investigations unveiled that ZIKV induces P62-mediated degradation of TRAF6, with NS1 identified as the primary contributor. Co-localization and interaction studies demonstrated that NS1 promotes the association of P62, a key autophagy mediator, with TRAF6. Notably, our findings revealed TRAF6 enhances ZIKV infection, NS1 ubiquitination, NS1 expression, and the production of inflammatory cytokines and chemokines. These insights highlight the intricate TRAF6-ZIKV relationship, offering potential for drug targeting NS1-TRAF6 interactions to manage ZIKV infections effectively.
研究领域:
病毒学
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免疫学
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分子生物学
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传染病学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2021
·Vol. 31
·期 25
·2101648
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IF 18.808
Zhen Wang,Dongmei Fu,Dazhi Xie,Shaoming Fu,Juanyan Wu,Shuanghu Wang,Fei Wang,Yicheng Ye,Yingfeng Tu,Fei Peng
Micro/nanomotors are attracting booming research enthusiasm with their revolutionary potential in biomedicine, sensing, and nanoengineering. Among the motors proposed, magnetic micro/nanomotors are of great interest with their high controllability and field biocompatibility. Yet the fabrication of magnetic actuated especially helical motors requires expensive and complicated instruments, 3D printing or glancing angle deposition, etc. Here, a soft and biocompatible helical poly(vinyl alcohol) (PVA) hydrogel motor via a versatile set-up is engineered. The obtained helical hydrogel motor offers high capacity for chemokine CXCL12 and superparamagnetic iron oxide (Fe 3 O 4 ) nanoparticles, which can then allow magnetic manipulation. With a low strength rotating magnetic field, the system is able to perform 3D precision navigation, necessary to steer the robotic system to a model diseased area. The chemokine cues from the hydrogel motor, acting as the synthetic leader cell, then directs immune T cell chemotactic migration. In a previously reported cell manipulating motor system, towing or pushing a single/two cell was demonstrated, with limited efficiency. This motor platform represents a novel approach for directing endogenous cell chemotaxis and organizing immune response.
研究领域:
生物医学工程
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免疫学
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纳米技术
✓ 已验证
DOI
高影响因子
Materials Today Bio
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2025
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IF 10.2
Yu Han,Xiufeng Jia,Yinwei Yang,Pei Guo,Chao Li,Yunze Zhang,Li Yin,Bo Jia,Haitao Wang
The development of bioactive scaffolds capable of orchestrating osteogenesis while modulating inflammatory responses remains a critical challenge in bone tissue engineering. To address this unmet need, we engineered a multifunctional composite scaffold through precise integration of poly(lactic-co-glycolic acid) (PLGA), type I collagen, zinc-imbued metal-organic frameworks (Zn-MOFs), and macrophage chemotactic factor (MCF) via extrusion-based 3D printing. Systematic biological assessments in vitro revealed the scaffold's remarkable osteoinductive capacity, evidenced by significant upregulation of alkaline phosphatase (ALP) activity (2.78±0.10 fold increase vs control, p<0.05) and enhanced collagen type I deposition (10.79±1.12 fold increase vs control, p<0.05) within 14 days of culture. In vivo implantation in rat femoral defect models demonstrated superior bone regeneration outcomes, with micro-CT analysis showing bone volume/ total volume (BV/TV) 31.39±3.04% compared to 16.44±3.26% in control (P<0.05). The Zn-MOF component mediated sustained release of Zn 2+ ions (cumulative release: 89.6±9.08% over 18 days). This dual-functional system synergistically combines MCF-driven cellular recruitment with Zn 2+ -mediated immunomodulation, creating a pro-regenerative microenvironment. Our findings not only demonstrate the feasibility of 3D-printed multi-material constructs for complex tissue engineering applications but also establish a new paradigm for developing smart biomaterials that concurrently address biological regeneration and inflammatory control.
研究领域:
生物医学工程
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组织工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
PeerJ
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2023
·
IF 2.7
Yuanchun Liu,Wanyi Huang,Huiyang Wang,Wei Lu,Jiayu Guo,Li Yu,Lina Wang
Bone marrow-derived mesenchymal stem cells (BMSCs) are increasingly being used in bone marrow transplantation (BMT) to enable homing of the allogeneic hematopoietic stem cells and suppress acute graft versus host disease (aGVHD). The aim of this study was to optimize the labelling of BMSCs with superparamagnetic iron oxide particles (SPIOs), and evaluate the impact of the SPIOs on the biological characteristics, gene expression profile and chemotaxis function of the BMSCs. The viability and proliferation rates of the SPIO-labeled BMSCs were analyzed by trypan blue staining and CCK-8 assay respectively, and the chemotaxis function was evaluated by the transwell assay. The expression levels of chemokine receptors were measured by RT-PCR and flow cytometry. The SPIOs had no effect on the viability of the BMSCs regardless of the labelling concentration and culture duration. The labelling rate of the cells was higher when cultured for 48 h with the SPIOs. Furthermore, cells labeled with 25 µg/ml SPIOs for 48 h had the highest proliferation rates, along with increased expression of chemokine receptor genes and proteins. However, there was no significant difference between the chemotaxis function of the labeled and unlabeled BMSCs. To summarize, labelling BMSCs with 25 µg/ml SPIOs for 48h did not affect their biological characteristics and chemotaxis function, which can be of significance for in vivo applications.
研究领域:
干细胞研究
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Small Science
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2023
·
IF 12.7
Maoze Wang,Ge Yan,Qiyao Xiao,Nan Zhou,Hao-Ran Chen,Wei Xia,Lihua Peng
Transdermal delivery of antigen and chemokine proteins that activates the maturation of skin dendritic cells (DCs) and direct the migration of activated DCs to lymph and spleen is an important alternative to conventional vaccines. However, stratum corneum forms a barrier to skin penetration. The poor cellular uptake of free antigens and chemokines also limits transcutaneous immunization efficacy. In this work, a pair of iontophoresis-driven microneedle patches is constructed, of which, two kinds of outer membrane vesicles (OMVs) derived from Escherichia coli transformed by plasmid encoding gp100 (IPMN-G) and chemokine ligand 21 (IPMN-C) are incorporated within microneedles, respectively. The topical application of IPMN-G and IPMN-C shows the effectiveness of transdermally delivering gp100 and CCL21 secreting vesicles to skin DCs. With iontophoresis as a driving generator, the release and uptake of transgenic OMVs in target cells are significantly enhanced, with transcutaneous immunization initiated. The in vivo applications of IPMN-G and IPMN-C with a 12 h interval retard the progression and prevent the occurrence of tumor spheroids. IPMN-GC is shown as a promising triplatform in engineering transgenic OMV-incorporated microneedles, driven by iontophoresis into a transcutaneous vaccine, providing a noninvasive system for the transdermal delivery of antigen and chemokine proteins for transcutaneous vaccination-meditated immunotherapy.
研究领域:
生物医学工程
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免疫学
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药学
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癌症研究
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产品关联
DOI
高影响因子
IMMUNITY
·
2019
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IF 21.522
Juan Liu,Xiaomin Zhang,Kun Chen,Yujie Cheng,Shuxun Liu,Meng Xia,Yali Chen,Ha Zhu,Zhiqing Li,Xuetao Cao
Summary CCR7 chemokine receptor stimulation induces rapid but transient dendritic cell (DC) migration toward draining lymph nodes, which is critical for the initiation of protective immunity and maintenance of immune homeostasis. The mechanisms for terminating CCR7-mediated DC migration remain incompletely understood. Here we have identified a long non-coding RNA lnc-Dpf3 whose feedback restrained CCR7-mediated DC migration. CCR7 stimulation upregulated lnc-Dpf3 via removing N6-methyladenosine (m 6 A) modification to prevent RNA degradation. DC-specific lnc-Dpf3 deficiency increased CCR7-mediated DC migration, leading to exaggerated adaptive immune responses and inflammatory injuries. Mechanistically, CCR7 stimulation activated the HIF-1α transcription factor pathway in DCs, leading to metabolic reprogramming toward glycolysis for DC migration. lnc-Dpf3 directly bound to HIF-1α and suppressed HIF-1α-dependent transcription of the glycolytic gene Ldha , thus inhibiting DC glycolytic metabolism and migratory capacity. We demonstrate a critical role for CCR7-inducible lnc-Dpf3 in coupling epigenetic and metabolic pathways to feedback-control DC migration and inflammatory responses.
研究领域:
免疫学
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分子生物学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2022
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IF 6.656
La Yi,Yaolong Zhou,Jingrong Song,Weifeng Tang,Hang Yu,Xi Huang,Hanlin Shi,Mengmeng Chen,Jing Sun,Ying Wei,Jingcheng Dong
Background Asthma is a chronic airway disorder with a hallmark feature of airflow obstruction that associated with the remodeling and inflammation in the airway wall. Effective therapy for controlling both remodeling and inflammation is still urgently needed. Leonuride is the main pharmacological component identified from Bu-Shen-Yi-Qi-Tang (BSYQT) which has been traditionally used in treatment of lung diseases. However, no pharmacological effects of leonuride in asthma were reported. Purpose Here we aimed to investigated whether leonuride provided a therapeutic efficacy in reversing asthma airway remodeling and inflammation and uncover the underlying mechanisms. Study design and methods Mouse models of chronic asthma were developed with ovalbumin (OVA) exposure for 8 weeks. Respiratory mechanics, lung histopathology and asthma-related cytokines were examined. Lung tissues were analyzed using RNA sequencing to reveal the transcriptional profiling changes. Results After oral administration with leonuride (15 mg/kg or 30 mg/kg), mice exhibited a lower airway hyperresponsiveness in comparison to asthmatic mice. Leonuride suppressed airway inflammation evidenced by the significant reductions in accumulation of inflammatory cells around bronchi and vessels, leukocyte population counts and the abundance of type 2 inflammatory mediators (OVA specific IgE, IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF). On the other hand, leonuride slowed down the process of active remodeling as demonstrated by weaker goblet cell metaplasia and subepithelial fibrosis in lung histopathology and lower transforming growth factor (TGF)-β1 levels in serum and BALF in comparison to mice treated with OVA only. Furthermore, we uncovered transcriptional profiling alternations in lung tissue of mice after OVA exposure and leonuride treatment. Gene sets belonging to type-2 cytokine/chemokine activity stood out in leonuride target transcripts. Those upregulated (Bmp10, Ccl12, Ccl22, Ccl8, Ccl9, Cxcl15, Il13, Il33, Tnfrsf9, Il31ra, Il5ra, Il13ra2 and Ccl24) or downregulated (Acvr1c and Il18) genes in asthmatic mice, were all reversely regulated by leonuride treatment. Conclusions Our results revealed the therapeutic efficacy of leonuride in experimental chronic asthma for the first time, and implied that its anti-inflammatory and antifibrotic properties might be mediated by regulation of type-2 high cytokine/chemokines responses.
研究领域:
药理学
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免疫学
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呼吸医学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Zunzhen Ming,Lin Han,Huanhuan Zhu,Meiyu Bao,Qiangyuan Fan,Shaobo Xue,Kesheng Wang,Yue Zhang,Meiling Lu,Chongshun Xu,Qi Wu,Tingting Li,Fenyong Sun
Bacterial endophthalmitis is a serious ocular infection and frequently results in vision loss or even blindness. Most of the present treatment methods are mainly embodied in strengthening the bactericidal effect, whereas the bacteria induced vigorous host immune response often leads to irreversible damage to eye tissue. Herein, we report an injectable hydrogel to treat endophthalmitis by killing invading bacteria and regulating ocular immunity. The designed hydrogel was formed by dynamic coordination crosslinking of sulfhydryl modified gelatin and silver ion while embedding the anti-CXCL1 antibody evenly. The injectable hydrogel can not only kill bacteria by releasing silver ions with its degradation, but also alleviate the bacteria-triggered excessive immune response via releasing anti-CXCL1 antibody to neutralize chemokine CXCL1, thus avoiding the host inflammatory response mediated bystander damage. Both in vitro and in vivo experiments showed that it has excellent ability against bacteria and immunomodulatory performance, preserving more integral retinal architecture and promoting visual recovery. This work may open up new avenues for combining antibacterial and immunotherapy in infectious endophthalmitis.
研究领域:
眼科学
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免疫学
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药学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Zhicheng Le,Yufeng Shou,Renee R. Li,Ling Liu,Runcheng Tan,Christopher John Charles,Zhijia Liu,Yongming Chen,Andy Tay
Persistent inflammation, characterized by the intense interplay of inflammatory chemokine secretion and immune cell infiltration, is a hallmark of many skin disorders including diabetic wounds and psoriasis with inadequate therapeutic interventions. Monocyte chemotactic protein-1 (MCP-1) is an inflammatory chemokine that plays a key role in recruiting and polarizing monocytes into pro-inflammatory macrophages to establish a vicious cycle that worsens the inflamed tissue microenvironment. Here, the sponge-like microneedles (HPMN) technology is described to alleviate inflammatory skin disorders. Heparin/4-arm PEG-NH 2 network crosslinked onto microneedle surface spatially attracted and sequestered multiple inflammatory chemokines including MCP-1. Enrichment of MCP-1 on microneedles recruits and traps inflammatory monocytes within the porous structure of microneedles. Subsequent removal of microneedles not only depletes inflammatory chemokine, MCP-1, but also its cellular source. As a result, HPMN treatment facilitates 47.1% smaller open wound area in mice and 27.2% shorter wound length in pigs. To demonstrate the versatility of the HPMN technology, it is also shown that combining the method with standard-of-care immunosuppressants reduces 45.1% epidermis thickening and attenuated immune cell influx in a mouse psoriasis model. Overall, the HPMN technology is a novel demonstration of employing inflammatory chemokine and cell extraction to treat a broad range of inflammatory skin disorders.
研究领域:
生物医学工程
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皮肤科
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炎症
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伤口愈合
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Bio
·
2023
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IF 8.2
Yuxiang Tang,WeiQi Yao,Hang Hu,Wei Xiong,Heng Mei,Yu Hu
TGF-β is widely existed in tumor microenvironment, taking part in tumorigenesis process including angiogenesis, cancer associated fibroblast (CAF) proliferation, and immunosuppression. It inhibited the activation, proliferation, migration and differentiation of T cells, in which way caused a limited therapeutic effects of chimeric antigen receptor T (CAR-T) towards solid tumor such as lymphoma. To targeted block TGF-β at tumor site, we take advantages of nano-techniques to deliver TGF-β inhibitors LY2157299 (LY) towards the tumor sites, in order to help achieve a improved and long-term functions of CAR-T towards lymphoma. Based on amphipathic hydroxyethyl starch-polycaprolactone (HES-PCL), LY and photosensitizer indocyanine green (ICG) were co-loaded in HES-PCL to achieve LY/ [email protected] nanoparticle. The enhanced function of CAR-T benefited from LY/ [email protected] were verified through lymphoma Raji cells in vitro and Nod scid gamma mice engrafted with the Raji cells in vivo. LY was targeted transported to tumor site and accelerated release by mild ICG photothermal. Chemokines CXCL9/10/11 at the tumor site relevant to CAR-T migration and chemokines receptor CXCR3 of CAR-T could be up-regulated by LY, thus facilitated the enhanced accumulation of CAR-T at lymphoma site. T effector memory cells differentiation could also be accelerated by LY/ [email protected] Combined therapy of LY/ [email protected] and CAR-T achieved 2.4 times higher antitumor activity and 2.7 times higher relapse inhibiting rates than CAR-T alone within 15 days and 11 days, respectively. The results suggested that LY/ [email protected] facilitated the enhanced therapeutic index of CAR-T cells towards lymphoma simply and safely, it may be further potentiated applied for other solid tumors.
研究领域:
肿瘤学
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免疫治疗
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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
危险品化学品经营许可证（带存储）