Journal of Functional Foods
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2020
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IF 3.701
Lvqi Zhou,Ning Hao,Xiaotian Li,Jiaxi Chen,Runyu Yang,Changqin Song,Yang Sun,Qi Zhang
In this study, we investigated the protective effect of Nattokinase (NK), the most active ingredient in natto used for healthcare, on dextran sulfate sodium (DSS)-induced chronic colitis and unraveled the potential mechanisms. NK dramatically attenuated clinical symptoms and pathological damage of DSS-induced chronic colitis. NK also inhibited proinflammatory cytokines production in DSS-induced colonic tissues. Mucosal integrity was maintained by NK. Moreover, nattokinase reversed DSS-induced decline of bacteria community diversity and intestinal microbial imbalance by decreasing levels of Firmicutes and increasing levels of Bacteroidetes . Tryptophan (Trp) metabolism analysis demonstrated that NK suppressed Trp catabolism especially the Kynurenine (Kyn) pathway in chronic colitis. Furthermore, NK strikingly down-regulated the protein expression of IDO-1 in chronic colitis mice. Taken together, the study demonstrated that NK relieved DSS-induced chronic colitis by regulating gut microbiota and suppressing Trp metabolism via inhibiting IDO-1. This study indicated that NK might be a promising and effective agent for IBD.
研究领域:
胃肠病学
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免疫学
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微生物学
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营养学
✓ 已验证
产品关联
DOI
高影响因子
Nanoscale
·
2025
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IF 5.1
Wentao Lei,Yinghui Wang,Tangyue Zheng,Qihang Wu,Hui Wen,Tingting Sun,Jun Liu,Zhigang Xie
It remains a clinical challenge to treat triple-negative breast cancer due to its aggressiveness and metastasis. Photothermal therapy (PTT) in combination with checkpoint blockade immunotherapy offers a promising strategy for such intractable tumors. In this study, a second near-infrared (NIR-II) photothermal agent (PCD NPs) and a tumor microenvironment-activatable nanoprodrug (NLG NPs) for indoleamine 2,3-dioxygenase 1 (IDO-1) blockade have been designed for the therapy of orthotopic triple-negative breast cancer. The NIR-II absorption of PCD NPs can guarantee the high penetration depth of the laser during PTT. At the same time, NLG NPs can be decomposed into the NLG919 monomer in the tumor microenvironment, which can effectively strengthen the immunogenic cell death-induced immune response. NIR-II PTT in synergy with IDO-1 blockade can effectively inhibit tumor growth and prevent tumor recurrence and metastasis. This work thus provides a safe, efficient and feasible method for the treatment of malignant tumors.
研究领域:
肿瘤学
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生物医学工程
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
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IF 15.8
Jingnan Li,Chengyan Luo,Tingyu Sun,Yinglin Zhou,Xinchang Huang,Dezhou Wu,Xirui Luo,Chao Zeng,Huanan Li
As a noninvasive treatment modality, high-intensity focused ultrasound (HIFU)-induced antitumor immune responses play a vital role in surgery prognosis. However, limited response intensity largely hinders postoperative immunotherapy. Herein, a hypoxia-specific metal–organic framework (MOF) nanosystem, coordinated by Fe3+, hypoxic-activated prodrug AQ4N, and IDO-1 signaling pathway inhibitor NLG919, is developed for the potentiating immunotherapy of HIFU surgery. The loaded AQ4N enhances the photoacoustic imaging effects to achieve accurate intraoperative navigation. Within the HIFU-established severe hypoxic environment, AQ4N is activated sequentially, following which it cooperates with Fe3+ to effectively provoke immunogenic cell death. In addition, potent NLG919 suppresses IDO-1 activity and degrades the immunosuppressive tumor microenvironment aggravated by postoperative hypoxia. In vivo studies demonstrate that the MOF-mediated immunotherapy greatly inhibits the growth of primary/distant tumors and eliminates lung metastasis. This work establishes a robust delivery platform to improve immunotherapy and the overall prognosis of HIFU surgery with high specificity and potency.
研究领域:
肿瘤学
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生物医学工程
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诊疗学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Neuroinflammation
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2024
·
IF 9.3
Kai Wang,Shufen Zhang,Yunxia Wang,Xiaomei Wu,Lijuan Wen,Tingting Meng,Xiangyu Jin,Sufen Li,Yiling Hong,Jia Ke,Yichong Xu,Hong Yuan,Fuqiang Hu
Background and purpose Neurodevelopmental disorders (NDDs) are characterized by abnormalities in brain development and neurobehaviors, including autism. The maternal–fetal interface (MFI) is a highly specialized tissue through which maternal factors affect fetal brain development. However, limited research exists on restoring and maintaining MFI homeostasis and its potential impact on NDDs. This study explores the role of placental indoleamine 2,3-dioxygenase (IDO-1) in MFI homeostasis and fetal brain development. Experimental Approach The maternal-fetal barrier was disrupted by sodium valproate (VPA) in pregnant mice, whose offspring show typical autism-like behaviors. Ultrastructural analysis and flow cytometric analysis were conducted to observe the morphological and immune system changes. Behavioral tests and immunofluorescence staining was used to investigate the ability and mechanism of taprenepag to alleviate the abnormal behaviors of VPA-exposed offspring and normalize the development of serotonergic neurons. Key results In VPA-exposed pregnant mice, the downregulation of IDO-1 led to maternal immune overactivation and disruption of maternal-fetal barrier, resulting in excessive 5-HT synthesis in the placenta. This process disrupted the development of the serotonergic neuronal system in the offspring, resulting in impaired development of serotonergic neurons, thalamocortical axons, and NDDs in the progeny. However, a single injection of taprenepag at E13.5 ultimately upregulated placental IDO-1 through amplifying the positive feedback loop COX-2/PGE 2 /PTGER-2/IDO-1 and abolished these alterations. Conclusion Taprenepag improved autism-like behaviors in the offspring of VPA-exposed mice by addressing placental IDO-1 downregulation. This study highlights the potential of targeting IDO-1 to mitigate MFI disruption and NDD development. Supplementary Information The online version contains supplementary material available at 10.1186/s12974-024-03300-7.
研究领域:
神经科学
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免疫学
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发育生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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