Gut Microbes
·
2025
·
IF 11
Yong Sun,Qiwen Wang,Yao Jiang,Jiamin He,Dingjiacheng Jia,Man Luo,Wentao Shen,Qingyi Wang,Yadong Qi,Yifeng Lin,Ying Zhang,Lan Wang,Liangjing Wang,Shujie Chen,Lina Fan
Gut microbes play a crucial role in regulating the tumor microenvironment (TME) of colorectal cancer (CRC). Nevertheless, the deep mechanism between the microbiota-TME interaction has not been well explored. In this study, we for the first time discovered that Lactobacillus intestinalis (L. intestinalis) effectively suppressed tumor growth both in the AOM/DSS-induced CRC model and the ApcMin/+ spontaneous adenoma model. Our investigation revealed that L. intestinalis increased the infiltration of immune cells, particularly dendritic cells (DC), in the TME. Mechanically, the tumor-derived CCL5 induced by L. intestinalis recruited DC chemotaxis through the NOD1/NF-κB signaling pathway. In clinical samples and datasets, we found positive correlation between L. intestinalis, CCL5 level, and the DC-related genes. Our study provided a new strategy for microbial intervention for CRC and deepened the understanding of the interaction between tumor cells and the immune microenvironment modulated by gut microbes.
研究领域:
肿瘤学
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微生物学
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免疫学
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DOI
PubMed
高影响因子
Frontiers in Cardiovascular Medicine
·
2024
·
IF 2.8
Yang Mengyue,Bi Wen,Zhang Zhijie
Background: The relationship between human immunodeficiency virus (HIV) infection and pulmonary arterial hypertension (PAH) has garnered significant scrutiny. Individuals with HIV infection have a higher risk of developing PAH. However, the specific mechanism of HIV-associated PAH remains unclear. Our study aims at investigating the shared biomarkers in HIV infection and PAH and predicting the potential therapeutic target for HIV-associated PAH.Methods: Data for HIV infection and PAH were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) analysis was performed to detect shared genes in HIV infection and PAH. Enrichment analysis was conducted to identify the function of common DEGs. Protein-protein interaction (PPI) analysis was used to detect key genes. These crucial genes were subsequently verified by RT-qPCR. Finally, candidate drugs were identified by using the Drug Signatures Database (DSigDB).Results: Nineteen common DEGs were identified in HIV infection and PAH. Enrichment analysis exhibited that the functions of these genes were mainly enriched in inflammatory responses, mainly including cellular immunity and interaction between viral proteins and cytokines. By constructing PPI networks, we identified the key gene CC-type chemokine ligand 5 (CCL5), and we verified that CCL5 was highly expressed in hypoxia induced human pulmonary artery endothelial cells (hPAECs) and human pulmonary artery smooth muscle cells (hPASMCs). In addition, we predicted 10 potential drugs targeting CCL5 by Autodock Vina.Conclusion: This study revealed that CCL5 might be a common biomarker of HIV infection and PAH and provided a new therapeutic target for HIV-associated PAH. However, further clinical validation is still indispensable.
研究领域:
免疫学
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分子生物学
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药理学
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生物信息学
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DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Jiaxing Huang,Xiaotang Wang,Na Li,Wei Fan,Xingran Li,Qian Zhou,Jiangyi Liu,Wanqian Li,Zhi Zhang,Xiaoyan Liu,Shuhao Zeng,Hui Yang,Meng Tian,Peizeng Yang,Shengping Hou
Activated microglia in the retina are essential for the development of autoimmune uveitis. Yin-Yang 1 (YY1) is an important transcription factor that participates in multiple inflammatory and immune-mediated diseases. Here, an increased YY1 lactylation in retinal microglia within in the experimental autoimmune uveitis (EAU) group is observed. YY1 lactylation contributed to boosting microglial activation and promoting their proliferation and migration abilities. Inhibition of lactylation suppressed microglial activation and attenuated inflammation in EAU. Mechanistically, cleavage under targets & tagmentation （CUT&Tag） analysis revealed that YY1 lactylation promoted microglial activation by regulating the transcription of a set of inflammatory genes, including STAT3, CCL5, IRF1, IDO1 , and SEMA4D . In addition, p300 is identified as the writer of YY1 lactylation. Inhibition of p300 decreased YY1 lactylation and suppressed microglial inflammation in vivo and in vitro. Collectively, the results showed that YY1 lactylation promoted microglial dysfunction in autoimmune uveitis by upregulating inflammatory cytokine secretion and boosting cell migration and proliferation. Therapeutic effects can be achieved by targeting the lactate/p300/YY1 lactylation/inflammatory genes axis.
研究领域:
免疫学
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神经科学
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分子生物学
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眼科学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2023
·
IF 29.4
Xiaoyu Yin,Lintao Wang,Yiming Niu,Daping Xie,Qingwen Zhang,Jian Xiao,Lei Dong,Chunming Wang
Hair loss affects over 50 million people worldwide with limited therapeutic options. Despite evidence highlighting the vital role of local immune cells in regulating the life cycle of hair follicles (HFs), accurate regulation of immunocytes to directly promote hair growth remains unachieved. Here, inspired by the physiological feedback in the skin immunity to suppress microbe-triggered inflammation, we develop an oligosaccharide biomaterial with “unmasked” specific activity to recruit T reg cells around HFs, leading to accelerated hair growth in mice. By processing the glucomannan polysaccharide via controllable enzymatic cleavage, we obtain a series of oligosaccharide fractions with more specific chemokine-inducing functions. Notably, a hexasaccharide-based fraction (OG6) stimulates macrophages to selectively express T reg -chemoattractant CCL5 through a mannose receptor-mediated endocytosis and NOD1/2-dependent signaling, as evidenced by molecular docking, inhibition assays, and a Foxp3 -reporter mouse model. Intradermal delivery of OG6 to the depilated mouse skin promotes T reg mobilization around HFs and stimulates de novo regeneration of robust hairs. Our study demonstrates that unmasking precise immunomodulatory functions in oligosaccharides from their parental polysaccharide can potentially solve the long-lasting dilemma with polysaccharide biomaterials that are widely renowned for versatile activities yet high heterogeneity, opening new avenues to designing glycan-based therapeutic tools with improved specificity and safety. This article is protected by copyright. All rights reserved
研究领域:
免疫学
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生物材料科学
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皮肤科
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药学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-14
·
IF 3.8
He Keting,Wei Dongfan,Liu Qiuhong,Liu Xiaoli,Zhou Diwenxin,Chen Shangci,Zhu Danhua,Xu Xiaowei
Acute liver injury (ALI) presents a challenging problem worldwide, prompting extensive research efforts. Cellular senescence has been found to be induced following ALI, and targeting cellular senescence has shown therapeutic potential. Therefore, understanding the expression of senescence-related genes in ALI can help to explore pathogenesis and treatment of this common disease. Carbon tetrachloride (CCl 4 ) is commonly used to study ALI. Although polymerase chain reaction (PCR) is a convenient and economical molecular biology technique widely used in basic medicine, research on selecting suitable reference genes to obtain objective and reproducible PCR data is scarce. Moreover, evidence supporting the choice of reference genes for experimental studies of CCl4-induced ALI and hepatic senescence in mice is limited. In this study, we obtained murine livers at four time points (0, 12, 24, and 48 h) following CCl4 treatment. We used five algorithms (geNorm, BestKeeper, NormFinder, delta Ct, and RefFinder) to rank 12 candidate genes in real-time reverse-transcription quantitative PCR (RT-qPCR) experiments. Focusing on cellular senescence in this model, we adopted four senescence-associated secretory phenotype (SASP) genes ( Il6 , Il1b , Ccl2 , and Ccl5 ) as target genes. Our results confirmed Gapdh and Tbp as suitable reference genes in murine CCl 4 -induced ALI models. Furthermore, we provide a table of published studies recommending reference genes for various liver disease models. This study provides a valuable reference for enhancing the reliability and reproducibility of ALI molecular findings.
研究领域:
分子生物学
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肝病学
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病理学
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基因组学
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产品关联
DOI
PubMed
高影响因子
Gut Microbes
·
2024
·
IF 12.2
Fangfang Chen,Songhe Guo,Yiqiu Li,Yongfan Lu,Le Liu,Shengxin Chen,Jun An,Ge Zhang
The intracellular bacterium Fusobacterium nucleatum (Fn) mediates tumorigenesis and progression in colorectal cancer (CRC). However, the origin of intratumoral Fn and the role of Fn-infected immunocytes in the tumor microenvironment remain unclear. Here, we observed that Fn-infected neutrophils/macrophages (PMNs/MΦs), especially PMNs, accumulate in tumor tissues and fecal Fn abundance correlates positively with an abundance of blood PD-L1+ PMNs in CRC patients. Moreover, Fn accumulates in tumor tissues of tumor-bearing mice via intragingival infection and intravenous injection. Mechanistically, Fn can survive inside PMNs by reducing intracellular ROS levels and producing H2S. Specifically, the lysozyme inhibitor Fn1792 as a novel virulence factor of Fn suppressed apoptosis of phagocytes by inducing CX3CR1 expression. Furthermore, Fn-driven CX3CR1+PD-L1+ phagocytes transfer intracellular Fn to tumor cells, which recruit PMNs/MΦs through the CXCL2/8-CXCR2 and CCL5/CCR5 axes. Consequently, CX3CR1+PD-L1+ PMNs infiltration promotes CRC metastasis and weakens the efficacy of immunotherapy. Treatment with the doxycycline eradicated intracellular Fn, thereby reducing the CX3CR1+PD-L1+ PMNs populations and slowing Fn-promoted tumor growth and metastasis in mice. These results suggest phagocytes as Fn-presenting cells use mutualistic strategies to home to tumor tissues and induce immunosuppression, and treatment with ROS-enhanced antibiotics can inhibit Fn-positive tumor progression.
研究领域:
肿瘤学
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免疫学
·
微生物学
·
药理学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2021
·
IF 9.776
Yudi Deng,Zhijie Jiang,Yincheng Jin,Jianan Qiao,Shan Yang,Hui Xiong,Jing Yao
Detrimental tumor microenvironment (TME) relies on distorted tumor vasculature for further tumor expansion. Vascular normalization therapy partly improves TME through vessel repairing, while these therapies enter an unbreakable Möbius ring due to each attempt hindered by pro-angiogenic factors from TME, leading to limited duration and extent of vascular normalization. Here, we developed a nanosystem including FLG and MAR/MPA nanodrugs to regulate both tumor vasculature and TME. FLG nanodrugs were constructed by connecting VEGF/VEGFR2 inhibitory low molecular weight heparin and gambogic acid with F3 peptide decoration for directly regulating on vascular endothelial cells and inducing vascular normalization. Meanwhile, MAR/MPA nanodrugs encapsulating CCL5/CCR5 blocker maraviroc were designed to restrict cytokine functions of angiogenesis and TME deterioration, contributing to vasculature repairing and TME reconstruction. Our results demonstrated this combined nanosystem synergistically induced vascular normalization window lasting 9 days and restored vascular permeability and oxygen supply in Panc-1 tumor. Furthermore, in melanoma, our nanosystem achieved immune improvements with increased infiltration of CD4 + and CD8 + T cells in a remodeled TME. The two nanodrugs assisting each other in terms of both vascular repairing and TME improvements successfully reversed the vicious crosstalk to a positive one, achieving overall TME remodeling and promoting therapeutic efficiency.
研究领域:
肿瘤学
·
纳米技术
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药理学
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免疫学
·
癌症生物学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Yao Wang,Lili Liu,Cheng Cheng,Shuxuan Wang,Qirui Zhai,Yunyang Song,Ronghua Dai
Zishen Pill (ZSP) is a traditional Chinese medicine that is frequently used to treat Benign Prostatic Hyperplasia (BPH), however its specific mechanism of action and active ingredients are yet unknown. We used a combination of serum pharmacochemistry and network pharmacology and a series of biochemical assays to explore the action mechanism of ZSP in the treatment of BPH. The BPH rat model was created using testosterone propionate , and following oral ZSP administration, the components of ZSP in rat serum were detected by UPLC-Q-Exactive Orbitrap/MS method. A "component-target-disease" network and PPI networks were constructed on this foundation. The primary mechanism of ZSP decreasing BPH in rats was studied by KEGG pathway and GO analysis. Finally, the potential pathways and key targets were further verified in vivo by molecular biology and immunological methods . 46 substances were charactered from rat serum, and 164 anti-BPH targets were screened from the database. According to network pharmacology, the primary targets were CASP3, STAT3, JUN, and PTGS2/COX2. Three related pathways (PI3K/Akt signaling pathway, AGE-RAGE signaling pathway and EGFR tyrosine kinase inhibitor resistance) were closely related to the therapeutic effects of ZSP. The findings of molecular biology demonstrated that ZSP may bring Bcl-2, BAX, CASP3, COX2, and 5LOX protein and gene expression in BPH rats appreciably closer to that of normal rats. Additionally, ZSP can lessen the expression of inflammatory cytokines in BPH rats, including VEGF, TNF-α, CCL5, and interleukin. Conclusion The above results suggest that ZSP may reduce BPH through inflammation/immunity and apoptosis/proliferation-related pathways. This study offers a fresh approach to investigate the basic pharmacological effects and mechanism of ZSP in the treatment of BPH.
研究领域:
药理学
·
中医药
·
分子生物学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
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