CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Pengyu Xue,Yinghan Wang,Xuefei Wang,Shilin Zhou,Xiaochen Wu,Lin Long,Chuanlong Guo
The incidence rate of breast cancer remains high, and lung metastasis often leads to treatment failure. Immunotherapy based on the cyclic guanosine monophosphate synthesis (cGAS) − interface gene stimulatory factor (STING) pathway is expected to bring benefits to the treatment of breast cancer. This study provided a delivery system based on fucoidan (Fu) and polyvinylpyrrolidone (PVP) for the potential molecule resveratrol (Res). The study confirmed that Fu and PVP were assembled into nanoparticles through hydrogen bonding and effectively loaded Res (Fu/PVP/Res). Interestingly, the adsorption of Zn 2+ (Fu/PVP/Res Zn 2+ ) was expected to provide impetus for the treatment of breast cancer. The results in vitro confirmed that Fu/PVP/Res Zn 2+ significantly inhibited the proliferation of breast cancer 4T1 cells, induced the accumulation of mitochondrial reactive oxygen species (ROS) and the damage of mitochondrial membrane potential (MMP), and further induced the cytoplasmic release of mtDNA, which was the direct cause of the activation of cGAS-STING pathway. In vivo studies confirmed that Fu/PVP/Res Zn 2+ treatment inhibited the growth of 4T1 transplanted tumors. Excitingly, Fu/PVP/Res Zn 2+ treatment also prevented lung metastasis of in situ tumors. The in vivo mechanism confirmed that Fu/PVP/Res Zn 2+ treatment activated the cGAS-STING pathway and induced abnormal expression of tumor apoptosis factors such as Bax/Bcl-2. In conclusion, our research provided potential for the treatment of breast cancer.
研究领域:
肿瘤学
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免疫学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Research
·
2023
·Vol. 27
·期 1
·1-16
·
IF 11.3
He Qingbin,Zheng Runxiao,Ma Junchi,Zhao Luyang,Shi Yafang,Qiu Jianfeng
Background The activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) signaling pathway has attracted great attention for its ability to up-regulate innate immune response and thus enhance cancer immunotherapy. However, many STING agonists limit the further advancement of immunotherapy due to weak tumor responsiveness or low activation efficiency. The responsive and effective activation of cGAS-STING signaling in tumors is a highly challenging process. Methods In this study, a manganese-based nanoplatform (MPCZ NPs) was constructed that could responsively and efficiently generate more manganese ions (Mn 2+ ) and reactive oxygen species (ROS) to activate cGAS-STING signaling pathway. Briefly, manganese dioxide (MnO 2 ) was loaded with zinc protoporphyrin IX (ZPP) molecule and coated by polydopamine (PDA) embedded with NH 4 HCO 3 to obtain MPCZ NPs. Additionally, MPCZ NPs were evaluated in vitro and in vivo for their antitumor effects by methyl thiazolyl tetrazolium (MTT) assay and TUNEL assays, respectively. Results In this system, tumor responsiveness was achieved by exogenous (laser irradiation) and endogenous (high levels GSH) stimulation, which triggered the collapse or degradation of PDA and MnO 2 . Moreover, the release of Mn 2+ augmented the cGAS-STING signaling pathway and enhanced the conversion of hydrogen peroxide (H 2 O 2 ) to hydroxyl radical (·OH) under NIR laser irradiation. Furthermore, the release of ZPP and the elimination of GSH by MPCZ NPs inhibited HO-1 activity and prevented ROS consumption, respectively. Conclusions This adopted open source and reduce expenditure strategy to effectively generate more ROS and Mn 2+ to responsively activate cGAS-STING signaling pathway, providing a new strategy for improving immunotherapy.
研究领域:
肿瘤学
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免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Shining Niu,Qian Chen,Lulu Yu,Xiao Wang,Haipeng Yu,Mei Wen,Zhigang Chen,Nuo Yu,Kun Li
Natural bacteria and bacterial bionics offer significant advantages in the synergistic approach to cancer treatments, while the development of such platforms remains challenging. Herein, bacterial membrane-coated chlorin e6-conjugated bacteriform manganese dioxide platform (BCBM) has been developed for amplifying phototherapeutic efficacy of tumors. The BCBM platform has been prepared by the in-situ growth of manganese dioxide on the surface of silica nanorods and subsequent etching process, photosensitizer conjugation, and bacterial membrane encapsulation. The manganese dioxide and bacterial membrane endow the BCBM with bacteria-like characteristics, enabling a specific response to the tumor microenvironment (TME). The manganese dioxide can react with hydrogen peroxide to produce large amounts of oxygen and manganese ions under acidic conditions. Upon near-infrared irradiation, the BCBM exhibits an excellent ability to generate reactive oxygen species because of sufficient oxygen supply. Furthermore, the released manganese ions activate cGAS-STING pathway, leading to the efficient apoptosis of cancer cells. The process of apoptosis is accompanied by the release of tumor-associated signaling molecules, which enhances therapeutic efficacy. Therefore, this work offers insights into designing biomimetic multifunctional nanoagents against cancers.
研究领域:
肿瘤学
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生物材料
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免疫治疗
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Lu Liu,Zhongxia Wang,Yulin Qi,Ang Huang,Caiping He,Xiaoyan Zhan,Xiaohe Xiao,Zhaofang Bai
Aberrant activation of the cGAS-STING pathway has been implicated in the pathogenesis of diverse inflammatory diseases. Kurarinone, a flavonoid compound isolated from Sophorae tonkinensis Radix et Rhizoma, has been reported to exhibit anti-inflammatory effects and is used to treat inflammatory diseases. But the effect of kurarinone on the cGAS-STING pathway has not been well studied. We aimed to investigate the impact of Kurarinone on cGAS-STING pathway activation and its protective effect against cGAS-STING-mediated inflammatory diseases. BMDMs and THP-1 cells pretreated with Kurarinone or vehicle were stimulated with ISD or various STING agonists; the protein level of p-IRF3 was analyzed by western blotting, and the secretion and mRNA level of inflammatory cytokines were detected by ELISA and qPCR, respectively. To further explore the potential targets and molecular mechanisms of Kurarinone, nucleocytoplasmic separation assays, STING oligomerization experiments, cellular thermal shift assays, drug affinity responsive target stability assays, and molecular docking were conducted. Additionally, DSS-induced inflammatory bowel disease and ConA-induced autoimmune hepatitis models were used to evaluate the effects of Kurarinone on cGAS-STING-mediated inflammatory diseases. In vitro, Kurarinone inhibited the phosphorylation of STING and IRF3, reduced IFNβ release, and downregulated the transcription of IFNβ, IL-1β, CXCL10, IL-6, TNF-α, and ISG15, in ISD-stimulated BMDMs and THP-1 cells. Additionally, Kurarinone suppressed IRF3 nuclear translocation, disrupted the interaction between STING and IRF3, but did not affect STING oligomerization. Furthermore, Kurarinone reduced the thermostability of STING while increasing its susceptibility to proteolytic degradation. The molecular docking results indicated a strong interaction between Kurarinone and STING. In vivo, Kurarinone attenuated the inflammatory response in DSS-induced inflammatory bowel disease and ConA-induced autoimmune hepatitis models by inhibiting cGAS-STING signaling activation. In conclusion, Kurarinone targets the STING protein to interfere with the interaction between IRF3 and STING, thereby inhibiting the activation of the cGAS-STING signaling pathway. Additionally, Kurarinone ameliorates inflammatory diseases by suppressing the cGAS-STING pathway. This study provides a potential candidate drug for the clinical treatment of STING-driven inflammatory diseases.
研究领域:
免疫学
·
分子生物学
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药理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Shaofeng Wang,Quanwei Li,Pan Guo,Luna Su,Tingyu Liang,Wenlan Yu,Qingwen Yang,Jianying Guo,Zhaoxin Tang,Jianzhao Liao
Terbuthylazine (TBA) is a widely employed pesticide that has been found to be a significant source of food and environmental pollution. Excessive exposure to TBA raises considerable apprehension regarding its potential impact on biological health, but its underlying toxic mechanisms have not been reported. Our findings indicated that TBA exposure could cause intestinal damage , as evidenced by decrease in the quantity of cupped cells and decrease in the expression of intestinal barrier-related proteins (Claudin-1, Occludin , ZO-1, and JAM-1). Additionally, exposure to TBA resulted in a significant decrease in the expression levels of oxidative stress-related genes and proteins. Furthermore, the expression of 8-hydroxy-2′-deoxyguanosine was significantly upregulated. Additionally, excessive exposure to TBA led to a substantial release of mitochondrial DNA, which further activated the cGAS-STING pathway and caused TBK1 and IRF3 phosphorylation. Meanwhile, mitophagy was activated under TBA exposure, as evidenced by decrease in the protein and gene levels of p62 and increase in the levels of PINK1 , PARKIN and LC3 II. Therefore, our results suggested that TBA exposure induced oxidative stress in the jejunum and caused mtDNA leakage, for activating the cGAS-STING pathway, which in turn promoted mitophagy . These findings revealed the toxicity mechanisms of TBA, which provided new insights into food safety caused by pesticide contamination.
研究领域:
毒理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yue Chen,Di Wu,Quan Li,Zhenghua Wei,Qian Liu,Jin Li,Daohui Gong,Chaowang Huang,Qianyi You,Hang Qian,Guansong Wang
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) cause severe lung inflammation and damage, compromising respiratory function. Nanomedicine offers hope in controlling this inflammation. DNA nanostructures, as drug carriers, stand out due to their non-toxic, programmable, and precisely controllable traits. However, they face challenges in physiological stability and functionalization as carriers. Here, we introduce TET AG , DNA tetrahedra assembled and functionalized with aminoguanidine without magnesium. Aminoguanidine not only aids tetrahedron assembly but also inhibits the cyclic GMP-AMP synthase and stimulator of interferon (cGAS-STING) pathway, a key inflammatory signal. By integrating STING siRNA into TET AG (TET AG -STING), we achieve synergistic anti-inflammatory effects in ALI/ARDS. Our results show that TET AG offers improved stability and cellular uptake. Importantly, TET AG -STING exhibits potent anti-inflammatory activity in vitro and in a Lipopolysaccharides-induced mouse model following intratracheal administration. This significantly improves lung injury scores and pulmonary functions. These findings underscore aminoguanidine’s therapeutic potential in ALI/ARDS and highlight the promise of DNA nanostructures in medical applications.
研究领域:
医学
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纳米医学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROPHARMACOLOGY
·
2025
·
IF 4.6
Hongqiao Wei,Yongxin Chen,Zhenmin Qin,Honglei Wang,Yujia Liu,Tang Song,Yong Wu,Wanxiang Hu,Xiaowei Huang,Guodong Lu,Jing Zhou
Artesunate, a derivative of artemisinin, has a variety of pharmacological effects. Its potential application in ischemic brain injury still largely unknown. This study investigated the therapeutic effect and pharmacological mechanism of artesunate in neuronal injury following cerebral ischemia, and explore the potential role of lysosomal function and cGAS-STING signaling pathway in ischemia injury and artesunate treatment. Studies in rat models have revealed that artesunate can ameliorate neuronal injury and improve learning and memory function following ischemic insults. Furthermore, both in vivo and in vitro studies have confirmed that artesunate can protect neural cells from ischemic injury-induced cell death. Mechanistically, artesunate appears to exert its neuroprotective actions by activating lysosomal function and inhibiting the cGAS-STING pathway-mediated imflammatory repsonse. Our findings provide valuable insights into the therapeutic effects of artesunate exerting a neuroprotective role in chronic ischemic brain injury by activating lysosomal function, inhibiting the cGAS-STING pathway, and regulating the inflammatory response. This study offers a potential therapeutic strategy by regulating lysosome for the treatment of stroke and related neurological disorders.
研究领域:
神经科学
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药理学
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2025
·Vol. 86
·期 3
·e70090
·
IF 4.2
Cailan Wang,Xinyi Lin,Shichun Guan,Qiaoyuan Wu,Shixiong Liang
Dihydroartemisinin (DHA) is a derivative of artemisinin, which affects inflammation, oxidative stress, and immune regulation. However, the mechanism underlying its effects remains largely unknown. This study aims to explore the mechanism by which DHA affects radiation-induced lung injury (RILI), providing new insights for lung radiotherapy. To elucidate its mechanism of action, C57BL/6 J mice were irradiated with 15 Gy whole chest. RILI was evaluated by qRT-PCR, ELISA, histology, Western blot analysis, immunohistochemistry, and RILI signaling cascade studies. In addition, small interfering RNAs were employed to knockdown cGAS proteins in the cGAS-STING signaling pathway in the human bronchial epithelium cell line (BEAS-2B). Both In Vivo and Vitro experiments were conducted to investigate the specific mechanism by which DHA alleviated RILI. We observed the activation of the cGAS-STING pathway, along with the phosphorylation of the downstream target NF-κB and an increase in inflammatory factor levels in the mouse model following radiation exposure. In the cell model, irradiation also triggered the activation of the cGAS-STING signaling pathway and its downstream targets, leading to elevated levels of inflammatory factors. Notably, knocking down the cGAS using small interfering RNA in the BEAS-2B cells significantly alleviated RILI in the cell model. Our study elucidated the mechanism of DHA reducing RILI through the cGAS/STING/NF-κB signaling pathway, and revealed that the GAS/STING/NF-κB axis may be a potential therapeutic target for RILI.
研究领域:
医学
·
药理学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2022
·
IF 6.1
Yuanxing Zhi,Jin Liu,Peihua Kuang,Xin Zhang,Ziwei Xu,Yanshan Chen,Xiuling Lin,Xiaoyan Wu,Pingzheng Zhou,Jianjun Chen
The enzyme cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA and catalyzes the formation of 2′3′-cyclic-GMP-AMP (cGAMP), which in turn triggers interferon (IFN) production. Inappropriate activation of cGAS and production of cGAMP have been linked to a diversity of autoimmune diseases. The volume-regulated anion channels (VRACs) have been recently demonstrated to permeate cGAMP, thus making the channel essential for the activation of the cGAS-cGAMP-STING axis. DCPIB, a prominent inhibitor of VRAC channel, has been recently reported to also significantly activate TREK1 channel. Herein, in this study, we have designed and synthesized a series of novel DCPIB derivatives and investigated their potential regulatory effects on VRAC/TREK1 channels. Our results manifested that compound 6u was a dual inhibitor of VRAC/TREK1 channels with IC 50 s of 7.11 ± 0.94 μM and 4.43 ± 0.90 μM, respectively. On top of that, our data demonstrated that 6u impaired interferon production in a concentration-dependently manner by dampening cGAS-cGAMP-STING pathway without any cytotoxicity when it comes to herpes simplex virus type 1 (HSV1) infection. To sum up, our study not only discovered a novel DCPIB analog with dual inhibitory effects on VRAC/TREK1 channels but also provided a new strategy for the design and development of newly potent VRAC inhibitors, which benefits the treatment of cGAS-STING related autoimmune and inflammatory diseases .
研究领域:
药理学
·
免疫学
·
分子生物学
·
化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Hua Chai,Renpeng Xia,Nan Ouyang,Jingyu Yao,Jiukun Hu,Minxuan Sun,Peng Miao
Reactive oxygen species (ROS) mediated cell damage is one of the most popular and effective ways for cancer therapy. However, overexpressed antioxidant of reduced glutathione (GSH) is always activated in tumor cells, which maintains redox equilibrium. Attempts to deplete GSH and elevate ROS levels can be potent therapeutic strategies. Herein, tumor cell membrane-encapsulated Fe 3 O 4 @MnO and 2′,3′-cyclic GMP-AMP (cGAMP) are prepared as the nanocatalyst for cancer therapy. The ionized Fe 3+ /Fe 2+ redox couple is utilized to initiate the Fenton reaction. Intracellular GSH level can thus be efficaciously controlled, and peroxide oxidation is catalyzed to produce excessive ROS. Meanwhile, cGAMP is released to trigger the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling axis. This targeted activation enhances the recruitment of macrophages, stimulates the secretion of critical pro-inflammatory cytokines, and consequently bolsters the efficacy of innate immune responses within the tumor microenvironment.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Xinyu Wang,Qingbin He,Lining Wang,Chengzhilin Li,Wenyu Zhang,Zhonghou Rong,Qingqing Yin,Yingchun Zhao
Sepsis, an inflammatory disease caused by bacterial infection, has become a global public health crisis. Excessive reactive oxygen species (ROS) in sepsis patients act as the primary trigger for activating intracellular immune pathways, ultimately leading to multiple organ dysfunction syndrome. The overexpression of acidic metabolites and ROS, characteristic of the infected microenvironment, significantly impedes sepsis treatment. Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, plays a key role in inflammatory diseases. The detrimental effects of STING in sepsis have been well documented. Here, we developed a pH-responsive nanotherapy platform (DMSNM@C-178/PAA) that combines ROS scavenging with cGAS-STING pathway inhibition for anti-inflammatory therapy. This nanoparticle is selectively released in the infected microenvironment, where reduced molybdenum-based polyoxometalates (Mo-POM) efficiently neutralize toxic ROS in vivo, while C-178 selectively inhibits the cGAS-STING pathway, thereby attenuating the inflammatory response and preventing organ deterioration. In vitro and in vivo studies demonstrate that DMSNM@C-178/PAA treats sepsis by eliminating excess ROS and modulating autoimmune dysfunction via the cGAS-STING pathway, providing a novel therapeutic strategy for sepsis management.
研究领域:
医学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
·
IF 3.4
Jingwen Xiao,Shilin Zhou,Fengshu Fei,Lin Long,Chuanlong Guo
Ulcerative colitis (UC) is a persistent intestinal disorder featuring periodic flare-ups of the colon's inner lining inflammation. Current therapeutic strategies, while effective in managing symptoms, are often limited by side effects and high costs. This study investigates the potential of pectin-loaded ferulic acid (PC-FA) nanoparticles as a novel therapeutic approach for UC, focusing on their ability to modulate the cGAS-STING pathway, a key mediator in the inflammation associated with UC. PC-FA nanoparticles were prepared and characterized for their physicochemical properties, antioxidant capacity, biocompatibility, and influence on the cGAS-STING pathway. In vitro experiments demonstrated that PC-FA nanoparticles enhanced the solubility and bioavailability of ferulic acid (FA), reduced oxidative stress, and protected colon epithelial cells from damage caused by the administration of dextran sulfate sodium (DSS). In vivo studies in a DSS-induced colitis mouse model showed that PC-FA nanoparticles mitigated weight reduction, lowered disease activity index (DAI) scores, and sustained colon length, and ameliorated histopathological changes. Additionally, PC-FA nanoparticles effectively targeted DNA damage and inhibited the cGAS-STING pathway, leading to a significant reduction in pro-inflammatory cytokines. Pharmacokinetic studies revealed rapid absorption of PC-FA in the bloodstream, with a predominant distribution in the intestines. The study concludes that PC-FA nanoparticles are a promising therapeutic strategy for UC, offering targeted drug delivery, enhanced bioavailability, and anti-inflammatory effects.
研究领域:
药理学
·
免疫学
·
消化系统疾病
✓ 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）