EMBO REPORTS
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2024
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IF 6.5
RenXiaoyu,ShiPeng,SuJing,WeiTonghua,LiJiayi,HuYiping,WuCongying
Tumor metastasis involves cells migrating directionally in response to external chemical signals. Reactive oxygen species (ROS) in the form of H2O2 has been demonstrated as a chemoattractant for neutrophils but its spatial characteristics in tumor microenvironment and potential role in tumor cell dissemination remain unknown. Here we investigate the spatial ROS distribution in 3D tumor spheroids and identify a ROS concentration gradient in spheroid periphery, which projects into a H2O2 gradient in tumor microenvironment. We further reveal the role of H2O2 gradient to induce chemotaxis of tumor cells by activating Src and subsequently inhibiting RhoA. Finally, we observe that the absence of mitochondria cristae remodeling proteins including the mitochondria-localized actin motor Myosin 19 (Myo19) enhances ROS gradient and promotes tumor dissemination. Myo19 downregulation is seen in many tumors, and Myo19 expression is negatively associated with tumor metastasis in vivo. Together, our study reveals the chemoattractant role of tumor microenvironmental ROS and implies the potential impact of mitochondria cristae disorganization on tumor invasion and metastasis.
研究领域:
肿瘤生物学
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细胞生物学
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医学
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DOI
PubMed
高影响因子
Materials Today Sustainability
·
2023
·
IF 7.8
Y. Jia,K. Wang,C. Li,S. Liu
Piezocatalysis, a new catalysis technology much relying on catalyst's piezoelectric property , attracts unprecedented research enthusiasm for applications in energy conversion and chemical synthesis, such as hydrogen peroxide production. However, the reported piezocatalytic activities are not ideal and one of the reasons is the unsatisfactory piezoelectricity , urging researchers to explore new and efficient piezocatalysts. Herein, the MAX phase materials (Ti 3 AlC 2 , Ti 3 AlCN, and Ti 3 SiC 2 ) are employed as piezocatalysts for hydrogen peroxide (H 2 O 2 ) and reactive oxygen species generation. Results suggest that Ti 3 SiC 2 possesses the highest piezocatalytic activity with a notable H 2 O 2 yield of 871.0 μmol/g/h accompanied with small amount of reactive oxygen species, while the Ti 3 AlC 2 and Ti 3 AlCN deliver relatively lower H 2 O 2 yields of 810.6 and 835.6 μmol/g/h in pure water, respectively. A series of characterizations and analysis have been employed to understand the insights of piezocatalytic activity difference and reaction mechanism. The enhanced peizocatalytic activity of Ti 3 SiC 2 can be traced to its notable piezoelectric property and reduced electronic transfer resistance as well as the improved free charge density, all of which are favorable factors benefiting the piezocatalytic H 2 O 2 generation. Moreover, H 2 O 2 production via piezocatalysis stems from both oxygen reduction and water oxidation .
研究领域:
材料科学
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催化化学
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能源转换
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DOI
高影响因子
BIOMATERIALS
·
2017
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IF 8.402
Jing-Jing Hu,Qi Lei,Meng-Yun Peng,Di-Wei Zheng,Yi-Xuan Chen,Xian-Zheng Zhang
Here, a positive feedback strategy was utilized to amplify the concentration of intracellular reactive oxygen species (ROS) and a ROS-triggered self-accelerating drug release nanosystem (defined as T/D@RSMSNs) was demonstrated for enhanced tumor chemotherapy. The mesoporous silica nanoparticles (MSNs) based nanocarriers were gated by β-cyclodextrin (β-CD) through the ROS-cleavable thioketal (TK) linker to encapsulate the anticancer drug doxorubicin hydrochloride (DOX) and ROS producing agent α-tocopheryl succinate (α-TOS), whose surface was further anchored with adamantane conjugated poly(ethylene glycol) chain (AD-PEG) via host-guest interaction. It was found that in human breast cancer (MCF-7) cells, T/D@RSMSNs could not only release DOX and α-TOS initiatively, but also lead to increased concentration of intracellular ROS, which could be used as new trigger to cut away TK linkage and then in turn facilitate the further release of DOX for enhanced chemotherapy. Both in vitro and in vivo experiments demonstrated that T/D@RSMSNs exhibited more significant antitumor activity in the human breast cancer than the traditional single-DOX loaded ROS-responsive nanocarrier. This novel ROS-triggered self-accelerating drug release nanosystem with remarkably improved therapeutic effects could provide a general strategy to branch out the applications of existing ROS-responsive drug delivery systems (DDSs).
研究领域:
肿瘤学
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药剂学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2022
·
IF 7.31
Tao Long,Qian Wu,Jing Wei,Yong Tang,Yan-Ni He,Chang-Long He,Xue Chen,Lu Yu,Chong-Lin Yu,Betty Yuen-Kwan Law,Jian-Ming Wu,Da-Lian Qin,An-Guo Wu,Xiao-Gang Zhou
Parkinson’s disease (PD) is a complex neurological disorder characterized by motor and nonmotor features. Although some drugs have been developed for the therapy of PD in a clinical setting, they only alleviate the clinical symptoms and have yet to show a cure. In this study, by employing the C. elegans model of PD, we found that ferulic acid (FA) significantly inhibited α-synuclein accumulation and improved dyskinesia in NL5901 worms. Meanwhile, FA remarkably decreased the degeneration of dopaminergic (DA) neurons, improved the food-sensing behavior, and reduced the level of reactive oxygen species (ROS) in 6-OHDA-induced BZ555 worms. The mechanistic study discovered that FA could activate autophagy in C. elegans, while the knockdown of 3 key autophagy-related genes significantly revoked the neuroprotective effects of FA in α-synuclein- and 6-OHDA-induced C. elegans models of PD, demonstrating that FA exerts an anti-PD effect via autophagy induction in C. elegans. Furthermore, we found that FA could reduce 6-OHDA- or H2O2-induced cell death and apoptosis in PC-12 cells. Moreover, FA was able to induce autophagy in stable GFP-RFP-LC3 U87 cells and PC-12 cells, while bafilomycin A1 (Baf, an autophagy inhibitor) partly eliminated the protective effects of FA against 6-OHDA- and H2O2-induced cell death and ROS production in PC-12 cells, further confirming that FA exerts an anti-PD effect via autophagy induction in vitro. Collectively, our study provides novel insights for FA as a potent autophagy enhancer to effectively prevent neurodegenerative diseases such as PD in the future.
研究领域:
神经科学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Food Chemistry-X
·
2022
·
IF 6.443
Lijuan Zhu,Wanfeng Hu,Ayesha Murtaza,Aamir Iqbal,Jiaxing Li,Jiao Zhang,Junjie Li,Mengjie Kong,Xiaoyun Xu,Siyi Pan
The potential mechanism behind the browning inhibition in fresh-cut water chestnuts (FWC) after eugenol (EUG) treatment was investigated by comparing the difference in browning behavior between surface and inner tissues. EUG treatment was found to inactivate browning-related enzymes and reduce phenolic contents in surface tissue. Molecular docking further confirmed the hydrophobic interactions and hydrogen bonding between EUG and phenylalanine ammonia-lyase (PAL). Moreover, EUG also enhanced reactive oxygen species (ROS)-scavenging enzyme activities, ultimately decreasing the O 2 - generation rates. Regarding inner tissue, EUG induced the accumulation of colorless phenolic compounds and increased the antioxidant capacity. In conclusion, 1.5 % EUG exhibited the best inhibitory effect on FWC browning, which partly attribute to the direct inhibitory effects on PAL activity. Furthermore, EUG could also enhance the enzymatic/non-enzymatic antioxidant capacity and alleviate the ROS damage to membranes, thereby, preventing the contact between oxidative enzymes and phenols and indirectly inhibiting the enzymatic browning in FWC.
研究领域:
食品科学
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植物生理学
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产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2022
·
IF 12.822
Bingling Zhong,Lin Zhao,Jie Yu,Ying Hou,Nana Ai,Jin-Jian Lu,Wei Ge,Xiuping Chen
Introduction The anti-cancer effect of high concentrations of ascorbic acid (AA) has been well established while its underlying mechanisms remain unclear. The association between iron and AA has attracted great attention but was still controversial due to the complicated roles of iron in tumors. Objectives Our study aims to explore the anti-cancer mechanisms of AA and the interaction between AA and iron in cancer. Methods The MTT and ATP assays were used to evaluate the cytotoxicity of AA. Reactive oxygen species (ROS) generation, calcium (Ca 2+ ), and lipid peroxidation were monitored with flow cytometry. Mitochondrial dysfunction was assessed by mitochondrial membrane potential (MMP) detection with JC-1 or tetramethylrhodamine methyl ester (TMRM) staining. Mitochondrial swelling was monitored with MitoTracker Green probe. FeSO 4 (Fe 2+ ), FeCl 3 (Fe 3+ ), Ferric ammonium citrate (Fe 3+ ), hemin chloride (Fe 3+ ) were used as an iron donor to investigate the effects of iron on AA’s anti-tumor activity. The in vivo effects of AA and iron were analyzed in xenograft zebrafish and allograft mouse models. Results High concentrations of AA exhibited cytotoxicity in a panel of cancer cells. AA triggered ROS-dependent non-apoptotic cell death. AA-induced cell death was essentially mediated by the accumulated intracellular Ca 2+ , which was partly originated from endoplasmic reticulum (ER). Surprisingly, exogenous iron could significantly reverse AA-induced ROS generation, Ca 2+ overloaded, and cell death. Especially, the iron supplements significantly impaired the in vivo anti-tumor activity of AA. Conclusions Our study elucidated the protective roles of iron in ROS/Ca 2+ mediated necrosis triggered by AA both in vitro and in vivo , which might shed novel insight into the anti-cancer mechanisms and provide clinical application strategies for AA in cancer treatment.
研究领域:
肿瘤学
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2021
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IF 10.588
Xinwei Li,Haiwei Li,Yu Huang,Junji Cao,Tingting Huang,Rong Li,Qian Zhang,Shun-cheng Lee,Wingkei Ho
To understand the conversion mechanism of photocatalytic gaseous formaldehyde (HCHO) degradation, strontium (Sr)-doped TiO 2– x –OV catalysts was designed and synthesized in this study, with comparable HCHO removal performance. Our results proved that foreign-element doping reduced Ti 4+ to the lower oxidation state Ti (4– x )+ , and that the internal charge kinetics was largely facilitated by the unbalanced electron distribution . Oxygen vacancies (OVs) were developed spontaneously to realize an electron-localized phenomenon in TiO 2– x –OV, thereby boosting O 2 adsorption and activation for the enhanced generation of reactive oxygen species (ROS). At the chemisorption stage, in-situ DRIFTS spectra and density functional theory calculation results revealed that surface adsorbed O 2 (O ads ) and lattice O (O lat ) engaged in the isomerisation of HCHO to dioxymethylene (DOM) on TiO 2– x –OV and TiO 2 , respectively. Time-resolved DRIFTS spectra under light irradiation revealed that the DOM was then converted to formate and thoroughly oxidized to CO 2 and H 2 O in TiO 2– x –OV. While bicarbonate byproducts were detected from DOM hydroxylation or possible side conversion of CO 2 in TiO 2 , owing to insufficient consumption of surface hydroxyl. Our study enhances the understanding on the photocatalytic oxidation of HCHO, thereby promoting the practical application in indoor air purification .
研究领域:
环境科学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 37
·8916-8925
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IF 7
Guiming Niu,Fucheng Gao,Can Li,Yandong Wang,Hui Li,Yanyan Jiang
Carbon dot (CD)-based nanozymes have great potential in antibacterial applications. In order to achieve enhanced broad-spectrum antibacterial capacity, we synthesized Co-doped drug-based CDs (Co-Lvx-CDs) using levofloxacin and vitamin B12 as precursors by mimicking the catalysis of antibacterial activity of natural enzymes. The Co-Lvx-CDs retained not only the effective functional groups of the traditional antibiotic levofloxacin but also achieved oxidase-like and peroxidase-like activities to generate reactive oxygen species (ROS) through Co doping. Additionally, the Co-Lvx-CDs had superb fluorescence properties and could be applied in information encryption. The CDs were validated to have a broad-spectrum bactericidal effect against Gram-positive and -negative bacteria, compensating for the limitations of levofloxacin while also having enhanced sterilization ability. Importantly, the proposed Co-Lvx-CDs provide a new idea for the design of multifunctional CD-based nanozymes with preconceived outcomes.
研究领域:
生物材料学
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医学微生物学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Chang Xu,Yue Feng,Xin-Xin Zhao,Shan Zhao,Shu-Guang Wang,Chao Song
Tetracycline (TC) and Cu(II) have been frequently detected in natural and engineering waters, especially in aquaculture water. However, literatures involving in the influence of Cu(II) on the transformation of TC are still insufficient. In this study, we investigated the photolytic fate of TC induced by Cu(II) under UV irradiation. Cu(II) significantly promoted the removal of TC with photolysis rate constant of 0.467 h −1 at TC:Cu(II) molar ratio = 1, which was 49.04% higher than that without Cu(II) (0.238 h −1 ). Cu(II) exhibited multiple influences on both direct and indirect photolysis of TC. Singlet oxygen ( 1 O 2 ) and hydroxyl radicals (·OH) made a major contribution to Cu(II)-induced TC photolysis, with contribution rates of 24.69% and 12.96%, respectively. Besides, Cu(II) preferred to complex between O20-O21 or O26-O27 to form TC-Cu(II) complexes with complexation ratio of 1. The Condensed Fukui Function and Condensed Double Descriptors values of TC-Cu(II) complexes were calculated for the first time with density functional theory. It showed that TC-Cu(II) complexes were more vulnerable to ROS attack, thus promoting TC degradation. Moreover, Cu(II) greatly changed the photolysis path of TC, mainly through hydroxylation, hydrogen extraction, and deamidation reaction into new byproducts. Furthermore, Cu(II) changed the toxicity of the products via changing the original TC photolysis products. This study provides new insights for the environmental fate of antibiotics, and also has far-reaching implications for wastewater treatment in pharmaceutical and aquaculture industry.
研究领域:
环境科学
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水处理工程
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产品关联
DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2024
·
IF 5.7
Jiahao Ni,Lichao Yu,Yixuan Wang,Tong Yang,Yueqi Bai,Bowen Zheng,Manshan Liang,Xiaoxia Ye,Yun-Yun Quan,Feifei Lin,Zu-Sheng Huang
Background Photodynamic therapy (PDT) is a pioneering and effective anticancer modality with low adverse effects and high selectivity. Hypochlorous acid or hypochlorite (HClO/ClO − ) is a type of inflammatory cytokine. The abnormal increase of ClO − in tumor cells is related to tumor pathogenesis and may be a “friend” for the design and synthesis of responsive phototherapy agents. However, preparing responsive phototherapy agents for all-in-one noninvasive diagnosis and simultaneous in situ therapy in a complex tumor environment is highly desirable but still remains an enormously demanding task. Results An acceptor-π bridge-donor-π bridge-acceptor (A-π-D-π-A) type photosensitizer TPTPy was designed and synthesized based on the phenothiazine structure which was used as the donor moiety as well as a ClO − responsive group. TPTPy was a multifunctional mitochondria targeted aggregation-induced emission (AIE) photosensitizer which could quickly and sensitively respond to ClO − with fluorescence “turn on” performance (19-fold fluorescence enhancement) and enhanced type I reactive oxygen species (ROS) generation to effectively ablate hypoxic tumor cells. The detection limit of TPTPy to ClO − was calculated to be 185.38 nM. The well-tailored TPTPy anchoring to mitochondria and producing ROS in situ could disrupt mitochondria and promote cell apoptosis. TPTPy was able to image inflammatory cells and tumor cells through ClO − response. In vivo results revealed that TPTPy was successfully utilized for PDT in tumor bearing nude mice and exhibited excellent biological safety for major organs. Significance and novelty A win-win integration strategy was proposed to design a tumor intracellular ClO − responsive photosensitizer TPTPy capable of both type I and type II ROS production to achieve photodynamic therapy of tumor. This work sheds light on the win-win integration design by taking full advantage of the characteristics of tumor microenvironment to build up responsive photosensitizer for in situ PDT of tumor.
研究领域:
癌症研究
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药学
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生物医学工程
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化学
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生物学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2023
·Vol. 27
·期 1
·108702-108702
·
IF 5.8
Hong-Yang Zhao,Kun-Heng Li,Dan-Dan Wang,Zhi-Li Zhang,Zi-Jian Xu,Ming-Hui Qi,Shi-Wen Huang
Immunogenic cell death (ICD) can activate the anticancer immune response and its occurrence requires high reliance on oxidative stress. Inducing mitochondrial reactive oxygen species (ROS) is a desirable capability for ICD inducers. However, in the category of ICD-associated drugs, numerous reported ICD inducers are a series of anthracyclines and weak in ICD induction. Herein, a mitochondria-targeting dihydroartemisinin derivative (T-D) was synthesized by conjugating triphenylphosphonium (TPP) to dihydroartemisinin (DHA). T-D can selectively accumulate in mitochondria to trigger ROS generation, leading to the loss of mitochondrial membrane potential (ΔΨ m ) and ER stress. Notably, T-D exhibits far more potent ICD-inducing properties than its parent compound. In vivo , T-D-treated breast cancer cell vaccine inhibits metastasis to the lungs and tumor growth. These results indicate that T-D is an excellent ROS-based ICD inducer with the specific function of trigging vigorous ROS in mitochondria and sets an example for incorporating artemisinin-based drugs into the ICD field.
研究领域:
肿瘤学
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免疫学
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药理学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Particle and Fibre Toxicology
·
2016
·Vol. 13
·期 1
·1-13
·
IF 8.649
Guo Hua,Zhang Jing,Boudreau Mary,Meng Jie,Yin Jun-jie,Liu Jian,Xu Haiyan
Background Administration of silver nanoparticles (AgNPs) to mice could result in their distribution and accumulation in multiple organs, with notable prominence in liver, lungs, and kidneys. However, how AgNPs transport through blood vesicular system to reach the target organs is unclear, and the precise differences in the mechanisms of toxicity between AgNPs and silver ions still remain elusive. In the present research, the pathological changes on these target organs with a focus on inter-endothelial junction was investigated to gain a new insight of AgNPs toxicity by comparing the mechanisms of action of AgNPs and AgNO3.Methods We investigated the in vitro cytotoxicity of either citrated-coated AgNPs (10, 75, and 110 nm) or silver nitrate (AgNO3) following 24 h incubations (1–40 μg/mL) in the presence of primary human umbilical vein endothelial cells (HUVEC). Meanwhile, we detected the effects of AgNPs on intercellular conjunction and intracellular ROS by VE-cadherin staining and 2′, 7′-dichlorodihydrofluorescein diacetate (DCFH-DA) assay, respectively. To assess in vivo toxicity, we administered single or multiple intravenous injections (25 μg Ag for AgNPs and 2.5 μg Ag for AgNO3 per dose) to mice.Results In the in vitro study, the TEM observation showed that AgNPs were taken up by endothelial cells while AgNO3 was taken up little. Meanwhile AgNPs incubation induced the elevation of intracellular ROS and down-regulation of VE-cadherin between the endothelial cells and affected the cytoskeleton actin reorganization, which could be rescued by antioxidant N-acetylcysteine. In contrast, AgNO3 caused direct cell death when the concentration was higher than 20 μg/mL and without ROS induction at lower concentration. The release of AgNPs from leaking vessels induced peripheral inflammation in the liver, lungs, and kidneys, and the severity increased in proportion to the diameter of the AgNPs used.Conclusion It is AgNPs but not AgNO3 that were taken up by vascular endothelial cells and induced intracellular ROS elevated, which was closely related to disruption of the integrity of endothelial layer. The AgNPs-induced leakiness of endothelial cells could mediate the common peripheral inflammation in liver, kidney and lung through intravenous exposure.
研究领域:
毒理学
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纳米技术
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细胞生物学
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药理学
✓ 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）