Science Advances
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2024
·Vol. 10
·期 40
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IF 11.7
Feng Zhang,Qiuyu Jiang,Jialiang Cai,Fansheng Meng,Wenqing Tang,Zhiyong Liu,Xiahui Lin,Wenfeng Liu,Yi Zhou,Xizhong Shen,Ruyi Xue,Ling Dong,Si Zhang
The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway in hepatocellular carcinoma (HCC) is limited. NOD-like receptors (NLRs) comprise a highly evolutionarily conserved family of cytosolic bacterial sensors, yet their impact on antitumor immunity against HCC remains unclear. In this study, we uncovered that NOD1, a well-studied member of NLR family, exhibits predominant expression in tumor-associated macrophages (TAMs) and correlates positively with improved prognosis and responses to anti–PD-1 treatments in patients with HCC. Activation of NOD1 in vivo augments antitumor immunity and enhances the effectiveness of anti–PD-1 therapy. Mechanistically, NOD1 activation resulted in diminished expression of perilipin 5, thereby hindering fatty acid oxidation and inducing free fatty acid accumulation in TAMs. This metabolic alteration promoted membrane localization of the costimulatory molecule OX40L in a lipid modification–dependent manner, thereby activating CD8+ T cells. These findings unveil a previously unrecognized role for NOD1 in fortifying antitumor T cell immunity in HCC, potentially advancing cancer immunotherapy.
研究领域:
肿瘤学
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免疫学
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癌症生物学
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DOI
PubMed
高影响因子
Protein & Cell
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2024
·
IF 13.6
Ma Wei,Zhang Lu,Chen Weilong,Chang Zhaoxia,Tu Juchuanli,Qin Yuanyuan,Yao Yuwen,Dong Mengxue,Ding Jiajun,Li Siqin,Li Fengkai,Deng Qiaodan,Yang Yifei,Feng Tingting,Zhang Fanrong,Shao Xiying,He Xueyan,Zhang Lixing,Hu Guohong,Liu Quentin,Jiang Yi-Zhou,Zhu Shu,Xiao Zhi,Su Dan,Liu Tong,Liu Suling
Tumor-resident microbiota in breast cancer promote cancer initiation and malignant progression. However, targeting microbiota to improve the effects of breast cancer therapy has not been investigated in detail. Here, we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis (ETBF) was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant chemotherapy. ETBF, albeit at low biomass, secreted the toxic protein BFT-1 to promote breast cancer cell stemness and chemoresistance. Mechanistic studies showed that BFT-1 directly bound to NOD1 and stabilized NOD1 protein. NOD1 was highly expressed on ALDH+ breast cancer stem cells (BCSCs) and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation, thereby activating the NOTCH1-HEY1 signaling pathway to increase BCSCs. NOD1 inhibition and ETBF clearance increases the chemosensitivity of breast cancer by impairing BCSCs.
研究领域:
肿瘤学
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微生物学
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分子生物学
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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
npj Science of Food
·
2025
·Vol. 9
·期 1
·1-13
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IF 7.8
Liu Ziwei,Li Hangyu,Yang Shuyao,Zhang Xinnan,Liu Qianqian,Xu Yuan,Yang Yanwen,Liao Yi,Wang Yao,Feng Haibo
A novel pectic polysaccharide with dual backbones (SHP-A, 15,866 Da) was isolated from Sinopodophyllum hexandrum fruits. This polysaccharide is a heteropolymer composed of six monosaccharides. Structural characterization based on nuclear magnetic resonance spectroscopy, methylation analysis, and other methods demonstrated that SHP-A features a unique architecture consisting of a rhamnogalacturonan-I backbone (alternating α-GalpA and α-Rha molecules with β-Galp/α-Araf side chains) and a β-glucomannan backbone (alternating β-Manp and β-Glcp molecules), interconnected via β-Galp bridges. Bioactivity assays showed that SHP-A exerts potent immunomodulatory effects by enhancing macrophage phagocytosis and nitric oxide release. Transcriptomics analyses and NOD1 inhibitor interventions confirmed that SHP-A can activate the NOD1/RIPK2/NF-κB axis and induce M1 polarization in RAW264.7 macrophages, thereby upregulating various cytokines and chemokines. Furthermore, SHP-A also appeared to enhance immune function through mitochondrial metabolism, which indicated its potential as an immunomodulatory agent that can be used in the development of immune-enhancing health foods in the future.
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PubMed
高影响因子
Gut Microbes
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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 Nutrition
·
2026
·
IF 5.1
Nairong Yao,Yiqian Xing,Ruobing Tang,Chunguang Xie,Qiyue Yang,Ya Liu,Xiyu Zhang
Background Shenqi compound (SQC) is an effective prescription in Chinese medicine to enhance glucose homeostasis and protect pancreatic cells from high glucose-induced damage. However, the protection mechanism remains unclear. Objective To investigate the effect of SQC on INS-1 cell secretion and evaluate the associated mechanisms. Methods INS-1 cells were cultured in serum augmented with or without NOD1 inhibitor ML130 (2μM) for 1 h, then exposed into a high glucose (50 mM) condition to simulate type 2 diabetes mellitus (T2DM) for 24 h and treated with different concentrations (0, 5, 10, 15, 20%) of SQC in serum for another 24 h. Then, the cell counting kit-8 (CCK-8) method, glucose-stimulated insulin secretion (GSIS) assay, transmission electron microscopy (TEM), real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blot were performed for further investigation. Results Under high glucose conditions, 15% SQC was the optimal therapeutic concentration, significantly improved INS-1 cell viability ( p = 0.032) and enhanced insulin secretion ( p < 0.0001). Ultrastructural analysis showed that after high glucose stimulation in GSIS, especially at 20 min, 15% SQC significantly increased both the total density ( p = 0.143) and the mature ratio ( p = 0.003) of insulin secretory vesicles. Furthermore, 15% SQC facilitated the dynamic transport of vesicles toward the cell membrane, evidenced by an increased vesicle density within 300 nm of the membrane at 10 min, followed by a subsequent decrease at 20 min—a trend consistent with that observed in the control group. Moreover, at the molecular level, 15% SQC intervention markedly up-regulated NOD1 and RIP2 protein expression ( p = 0.029 and p < 0.0001) and transcription ( p = 0.886 and p = 0.393) levels, while ML130 reversed the activation of the NOD1/RIP2 pathway. Conclusions SQC promotes the maturation and transport of insulin secretory vesicles, thereby enhancing the secretory function of INS-1 cells in response to high glucose-induced damage. This protective effect may be associated with the activation of the NOD1/RIP2 signaling pathway.
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高影响因子
Foods
·
2024
·Vol. 13
·期 21
·3354
·
IF 4.7
Weiwei Wu,Zhiqiang Zheng,Zhihui Wang,Chenxi Gao,Yilin Liang,Wen Zeng,Weijiang Sun
Diabetes remains a critical global public health challenge, posing a growing threat to human health and well-being. White tea is a lightly fermented tea and one of the six traditional tea categories in China. Owing to its rich content of bioactive compounds such as catechins and alkaloids, it has demonstrated potential anti-diabetic properties. However, its precise bioactive components, mechanisms of action, and relevant molecular targets require further investigation. In this study, an integrated approach combining polyphenol-targeted metabolomics, in vitro antioxidant assays,α-glucosidase inhibition tests, network pharmacology analysis, GEO database exploration, molecular docking, and molecular dynamics simulations was employed to identify the potential anti-diabetic compounds, targets, and mechanisms of white tea. The findings revealed that white tea is particularly abundant in 10 bioactive compounds, including epigallocatechin gallate, epicatechin gallate, and catechin, all of which exhibit significant anti-diabetic potential. These compounds were found to exert their effects by interacting with core molecular targets, namely cathepsin V (CTSV) and nucleotide-binding oligomerization domain-containing protein 1 (NOD1), and engaging in pathways related to signal transduction, apoptosis, and immune responses. This study establishes a strong theoretical basis for advancing white tea research and underscores new opportunities for applying natural products in diabetes therapy.
研究领域:
药理学
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代谢组学
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生物信息学
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计算生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）