ANALYTICA CHIMICA ACTA
·
2024
·
IF 5.7
Zhirong Geng,Miaomiao Zhang,Binghuan Huang,Xiaohong Zhang,Zhilin Wang
Background Adenosine 5′-triphosphate (ATP) plays an important role in cell metabolism and has been regarded as an indicator of cell survival and damage. Golgi apparatus participates in the signal transduction processes of substance transport, ion homeostasis and stress when extracellular substances enter cells. Till now, there is no fluorescent probe for monitoring Golgi ATP level fluctuation and visualizing the configuration change of the Golgi apparatus during the inhibition of glycolysis. Results Herein, we report the synthesis of a novel water-soluble cationic polythiophene derivative ( PEMTEA) that can be employed as a fluorescent sensor for measuring ATP in the Golgi apparatus. PEMTEA self-assembles into PT-NP nanoparticles in aqueous solution with a diameter of approximately 2 nm. PT-NP displays high sensitivity and superb selectivity towards ATP with a detection limit of 90 nM and a linear detection range from 0 to 3.0 μM. The nanoparticles show low toxicity to HepG2 cells and good photostability in the Golgi apparatus. With the stimulation of Ca 2+ , PT-NP was practically applied to real-time monitor of endogenous ATP levels in the Golgi apparatus through fluorescence microscopy. Finally, we studied the relationship between the concentration of ATP and configuration of the Golgi apparatus during the inhibition of glycolysis using PT-NP . Significance We have demonstrated that PT-NP can not only indicate the fluctuation and distribution of ATP in the Golgi apparatus, but also give the information of the configuration change of the Golgi apparatus at the single-cell level during the inhibition of glycolysis.
研究领域:
细胞生物学
·
生物化学
·
医学
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DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Xiaozhao Wang,Jing Li,Zhengtao Luo,Zhimin Gao,Yongxin Huang,Jiamin Luo,Xinyi Wang,Yaru Zhang,Meiling Tan,Zhiyao Hou
Insufficient adenosine triphosphate (ATP) can reduce the synthesis of heat-stress-induced heat shock proteins (HSPs) to promote the efficiency of mild photothermal therapy (mPTT), thus the rational design of ATP-exhausted strategy based on nanotechnology is an effective approach to resuscitate mPTT. Herein, Nd 3+ doped nanocrystals (NaYF 4 :Nd@CaF 2 , Nd-NCs) modified hollow mesoporous manganese oxide (H-MnO x ) nanocomposite (H-MnO x @Nd-NCs, MN) is synthesized, and loaded with glucose transporters (GLUTs) inhibitor KL-11743, noted as MN-KL nanozyme. In tumor microenvironment (TME), MN-KL can react with overexpressed glutathione (GSH) to release KL-11743, which can suppress the synthesis of intracellular ATP at the source by blocking glucose uptake to inhibit HSPs expression, meanwhile, MN-KL catalyzes the production of ·O 2 − / 1 O 2 /·OH and lipid peroxidation (LPO) to cleave existing HSPs. Through a two-pronged strategy with ATP inhibition and oxide accumulation, reducing the level of HSPs can be guaranteed for achieving efficient mPTT in both subcutaneous and in situ tumor models in mice. During this process, Nd-NCs can absorb near-infrared light and convert it into heat, and the quenched fluorescence of Nd-NCs by H-MnO x can be recovered through GSH-triggered biodegradation in tumors, thus the modification of Nd-NCs not only provides photothermal effect but also enables MN to own TME-activated fluorescence imaging.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL BOTANY
·
2023
·
IF 6.9
He Chengyong,Xing Fei,Liang Jiahui,Zhang Zhixiang,Zhan Binhui,Habili Nuredin,Wang Hongqing,Li Shifang
Apple necrotic mosaic virus (ApNMV) is associated with apple mosaic disease in China. However, the mechanisms of ApNMV infection, as well as host defence against the virus, are still poorly understood. Mitochondrial ATP synthase plays a fundamental role in the regulation of plant growth and development. However, mitochondrial ATP synthase function in response to virus infection remains to be defined. In the present study, a yeast two-hybrid (Y2H) screening revealed that the apple mitochondrial ATP synthase oligomycin sensitivity-conferring protein (OSCP) subunit (MdATPO) interacts with ApNMV coat protein (CP). It was further verified that overexpression of MdATPO in Nicotiana benthamiana inhibited viral accumulation. In contrast, silencing of NbATPO facilitated viral accumulation, indicating that ATPO plays a defensive role during ApNMV infection. Further investigation demonstrated that ApNMV infection accelerated abscisic acid (ABA) accumulation, and ABA negatively regulated ATPO transcription, which was related to the ability of ABA insensitive 5 (ABI5) to bind to the ABA-responsive elements (ABREs) of the ATPO promoter. Taken together, our results indicated that transcription factor ABI5 negatively regulated ATPO transcription by directly binding to its promoter, leading to the susceptibility of apple and N. benthamiana to ApNMV infection. The current study facilitates a comprehensive understanding of the intricate responses of the host to ApNMV infection.
研究领域:
植物病理学
·
分子生物学
·
病毒学
·
植物生理学
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2021
·
IF 3.503
Danling Liang,Tianqiao Yong,Xue Diao,Shaodan Chen,Diling Chen,Chun Xiao,Dan Zuo,Yizhen Xie,Xinxin Zhou,Huiping Hu
Context Poria coco F.A.Wolf (Polyporaceae) dispels dampness and promotes diuresis implying hypouricaemic action.Objective To examine hypouricaemic action of Poria coco.Materials and methods Ethanol extract (PCE) was prepared by extracting the sclerotium of P. cocos with ethanol, and the water extract (PCW) was produced by bathing the remains with water. PCE and PCW (50, 100 and 200 mg/kg, respectively) were orally administered to hyperuricemic Kunming mice (n = 8) to examine its hypouricaemic effect. Also, molecular docking was performed.Results P. cocos showed excellent hypouricaemic action, decreasing the serum uric acid of hyperuricaemia (HUA) control (526 ± 112 μmol/L) to 178 ± 53, 153 ± 57 and 151 ± 62 μmol/L (p < 0.01) by PCE and 69 ± 23, 63 ± 15 and 62 ± 20 μmol/L (p < 0.01) by PCW, respectively. According to SCrs, BUNs and H&E staining, PCE and PCW partially attenuated renal dysfunction caused by HUA. They presented no negative effects on ALT, AST and ALP activities. They elevated ABCG2 (ATP-binding cassette super-family G member 2) mRNA and protein expression in comparison to HUA control. In molecular docking, compound 267, 277, 13824, 15730 and 5759 were predicted as the top bioactives of P. cocos against HUA, which even presented better scores than the positive compound, oestrone 3-sulfate.Discussion and conclusions This paper demonstrated the hypouricaemic and nephroprotective effects of P. cocos in hyperuricemic mice by up-regulating ABCG2. These results may be useful for the development of a hypouricaemic agent.
研究领域:
药理学
·
分子生物学
·
中医
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产品关联
DOI
PubMed
高影响因子
CELL CALCIUM
·
2018
·
IF 3.718
Bin Liu,Wanxin Cao,Jiping Li,Jun Liu
Adenosine triphosphate (ATP) is stored as lysosomal vesicles in marginal cells of the stria vascular in neonatal rats, but the mechanisms of ATP release are unclear. Primary cultures of marginal cells from 1-day-old Sprague–Dawley rats were established. P2Y 2 receptor and inositol 1,4,5-trisphosphate (IP3) receptor were immunolabelled in marginal cells of the stria vascular. We found that 30 μM ATP and 30 μM uridine triphosphate (UTP) evoked comparable significant increases in the intracellular Ca 2+ concentration ([Ca 2+ ] i ) in the absence of extracellular Ca 2+ , whereas the response was suppressed by 100 μM suramin, 10 μM 1-(6-(17β-3-methoxyester-1,3,5(10)-trien-17-yl)amino)-hexyl)-1H-pyrrole-2,5-dione(U-73122), 100 μM 2-aminoethoxydiphenyl borate (2-APB) and 5 μM thapsigargin (TG), thus indicating that ATP coupled with the P2Y 2 R-PLC-IP3 pathway to evoke Ca 2+ release from the endoplasmic reticulum (ER). Incubation with 200 μM Gly-Phe-β-naphthylamide (GPN) selectively disrupted lysosomes and caused significant increases in [Ca 2+ ] I ; this effect was partly inhibited by P2Y 2 R-PLC-IP3 pathway antagonists. After pre-treatment with 5 μM TG, [Ca 2+ ] i was significantly lower than that after treatment with P2Y 2 R-PLC-IP3 pathway antagonists under the same conditions, thus indicating that lysosomal Ca 2+ triggers Ca 2+ release from ER Ca 2+ stores. Baseline [Ca 2+ ] i declined after treatment with the Ca 2+ chelator 50 μM bis-(aminophenolxy) ethane- N , N , N ʹ, N ʹ-tetra-acetic acid acetoxyme-thyl ester (BAPTA-AM) and 4 IU/ml apyrase. 30 μM ATP decrease of the number of quinacrine-positive vesicles via lysosome exocytosis, whereas the number of lysosomes did not change. However, lysosome exocytosis was significantly suppressed by pre-treatment with 5 μM vacuolin-1. Release of ATP and β-hexosaminidase both increased after treatment with 200 μM GPN and 5 μM TG, but decreased after incubation with 50 μM BAPTA-AM, 4 IU/ml apyrase and 5 μM vacuolin-1. We suggest that ATP triggers Ca 2+ release from the ER, thereby contributing to secretion of lysosomal ATP via lysosomal exocytosis. Lysosomal stored Ca 2+ triggers Ca 2+ release from the ER directly though the IP3 receptors, and lysosomal ATP evokes Ca 2+ signals indirectly via the P2Y 2 R-PLC-IP3 pathway.
研究领域:
细胞生物学
·
神经科学
·
生理学
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产品关联
DOI
PubMed
高影响因子
Molecular Catalysis
·
2020
·
IF 3.687
Caixia Cui,Hong Ming,Linjing Li,Mingjie Li,Jian Gao,Tao Han,Yunyun Wang
We report here adopting a glucose template for synthesizing mesoporous silica for enzyme in-situ immobilization. Bifunctional GSH synthetase (GSHF) and polyphosphate kinase (PPK) were selected as model system for synthesizing GSH with ATP regeneration. Results indicated that a pore size that was slightly smaller than that of enzyme was responsible for the high performance of immobilized enzyme inside mesoporous without protein leaking. Then, the cationic dopamine was used for PPK immobilization by self-polymerization. The co-immobilized enzyme activity was much higher than that of the free enzyme. The catalytic efficiency kcat/Km of co-immobilized enzyme was higher than that of the free enzyme (8.5 and 1.5 times higher for GSHF and PPK, respectively). After optimizing the reaction parameters, the co-immobilized enzymes exhibited excellent operational and storage stability, and could be re-used seven times and retained the original activity after 30 days. It is hoped that these findings will pave the way for applying enzyme co-immobilization to biocatalytic system.
研究领域:
生物化学
·
生物技术
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
BIOMACROMOLECULES
·
2018
·
IF 5.738
Cuiping Jiang,Zitong Qi,Hengbo Jia,Yilei Huang,Yunbo Wang,Wenli Zhang,Zimei Wu,Hu Yang,Jianping Liu
In this work, we report on an ATP-responsive low-molecular-weight polyethylenimine (LMW-PEI)-based supramolecular assembly. It formed via host–guest interaction between PEI (MW = 1.8 kDa)-α-cyclodextrin (α-CD) conjugates and PEI1.8k-phenylboronic acid (PBA) conjugates. The host–guest interaction between PEI1.8k-α-CD and PEI1.8k-PBA was confirmed by the 2D-NOESY chromatogram experiment and competition test. The ATP-responsive property of the supramolecular assembly was evaluated by a series of ATP-triggered degradation and siRNA release studies in terms of fluorescence resonance energy transfer, agarose gel electrophoresis assay, and the time course monitoring of the particle size and morphology. Confocal laser scanning microscopy confirmed the intracellular disassembly of the supramolecular polymer and the release of siRNA. The supramolecular assembly showed high buffering capability and was capable of protecting siRNA from RNase degradation. It had high cytocompatibility according to in vitro cytotoxicity and hemolysis assays. LMW-PEI-based supramolecular assembly facilitated cellular entry of siRNA via energy-dependent endocytosis. Moreover, the assembly/SR-A siRNA polyplexes at N/P ratio of 30 was most effective in knocking down SR-A mRNA and inhibiting uptake of modified LDL. Taken together, this work shows that ATP-responsive LMW-PEI-based supramolecular assembly is a promising gene vector and has potential application in treating atherosclerosis.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2022
·
IF 14.903
Jiulong Zhang,Xiaoyan Sun,Xiufeng Zhao,Chunrong Yang,Menghao Shi,Benzhuo Zhang,Haiyang Hu,Mingxi Qiao,Dawei Chen,Xiuli Zhao
Amplifying “eat me signal” during tumor immunogenic cell death (ICD) cascade is crucial for tumor immunotherapy. Inspired by the indispensable role of adenosine triphosphate (ATP, a necessary “eat me signal” for ICD), a versatile ICD amplifier was developed for chemotherapy-sensitized immunotherapy. Doxorubicin (DOX), ATP and ferrous ions (Fe 2+ ) were co-assembled into nanosized amplifier (ADO-Fe) through π‒π stacking and coordination effect. Meanwhile, phenylboric acid-polyethylene glycol-phenylboric acid (PBA-PEG-PBA) was modified on the surface of ADO-Fe (denoted as PADO-Fe) by the virtue of d -ribose unit of ATP. PADO-Fe could display active targetability against tumor cells via sialic acid/PBA interaction. In acidic microenvironment, PBA-PEG-PBA would dissociate from amplifier. Moreover, high H 2 O 2 concentration would induce hydroxyl radical (·OH) and oxygen (O 2 ) generation through Fenton reaction by Fe 2+ . DOX and ATP would be released from the amplifier, which could induce ICD effect and “ICD adjuvant” to amplify this process. Together with programmed death ligands 1 (PD-L1) checkpoint blockade immunotherapy, PADO-Fe could not only activate immune response against primary tumor, but also strong abscopal effect against distant tumor. Our simple and multifunctional ICD amplifier opens a new window for enhancing ICD effect and immune checkpoint blockade therapy.
研究领域:
肿瘤学
·
免疫学
·
化疗
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2022
·Vol. 14
·期 10
·3808-3817
·
IF 8.307
Xi-Xi Chen,Mei-Jia Hou,Wen-Xin Wang,Min Tan,Zhi-Ke Tan,Guo-Jiang Mao,Bin Yang,Yongfei Li,Chun-Yan Li
Cancer is a major public health problem worldwide, and traditional chemotherapy or a single therapeutic strategy often fails to achieve expected results in cancer treatment. Thus, the development of a method to realize controlled drug delivery and synergistic therapy is required. Herein, MOF-based nanoparticles named RhI–DOX–GOD@ZIF-90 are synthesized using RhI (a near-infrared fluorescent dye), DOX (an anti-cancer drug) and GOD (glucose oxidase). RhI and DOX are encapsulated inside the ZIF-90 framework and GOD is loaded on the surface of ZIF-90. Owing to the fact that the ATP level in cancer cells is abnormally higher than that in normal cells, RhI–DOX–GOD@ZIF-90 nanoparticles are destructed only in cancer cells. RhI is released to give outstanding NIR emission and realize controlled drug delivery. DOX is released and cancer cells are killed by chemotherapy. Also, GOD is released to consume glucose and achieve the purpose of starving the cancer cells. By making full use of the advantages of near-infrared emission, RhI–DOX–GOD@ZIF-90 nanoparticles can be used to image ATP in tumor-bearing mice. At the same time, DOX and GOD can be released accurately at tumor sites of mice and excellent anti-tumor efficiency by synergistic chemotherapy and starvation therapy is achieved.
研究领域:
癌症治疗
·
纳米技术
·
药理学
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYST
·
2020
·Vol. 145
·期 14
·5032-5040
·
IF 3.978
Jie Lv,Shuangling Wang,Cong Zhang,Yulong Lin,Yan Fu,Meng Li
Breaking the pH limitation of the enzyme-like activity of nanomaterials is of great importance for extending their applications in environmental and biomedical fields. Herein, to mimic the role of histidine residues in horseradish peroxidase (HRP), adenosine 5′-triphosphate (ATP) is reported to improve the peroxidase-like activity of hollow Prussian blue nanocubes (hPBNCs). Due to the inherited porous structures, hPBNCs can expose all the binding sites as far as possible to ATP to significantly amplify their catalytic activity and broaden their applicable pH range up to pH 12. Introduction of ATP provides the possibility of realizing efficient catalytic reactions under alkaline conditions. Upon binding with hPBNCs, ATP can enhance the stability of hPBNCs, increase the affinities of the catalysts towards substrates and improve the conductivity of hPBNCs as well as change the decomposed product from H2O2. Moreover, on the basis of the different catalytic activities of hPBNCs towards ATP, adenosine 5′-diphosphate and adenosine 5′-monophosphate, hPBNCs–ATP is utilized to construct a novel colorimetric sensor for the detection of alkaline phosphatase (ALP) activity in biological fluids, which is significantly important for the clinical diagnosis of ALP-related diseases.
研究领域:
纳米材料
·
生物化学
·
催化
·
医学诊断
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 22
·7456-7470
·
IF 6.843
Xiangyu Meng,Jia Song,Yunfeng Lei,Xuezhong Zhang,Zhixin Chen,Zhuoxuan Lu,Liming Zhang,Zhifei Wang
Severe hypoxia in solid tumors limits the efficacy of oxygen (O2)-dependent photodynamic therapy (PDT). The overexpressed heat shock proteins (HSPs) in tumor cells hamper the effect of photothermal therapy (PTT). Herein, a tumor oxygenation-enhanced and ATP-reduced gelatin nanoreactor (MCGPD ∼ RGD NPs) for PDT/PTT-augmented combination cancer therapy is reported. In this nanosystem, the Arg-Gly-Asp (RGD) peptides of MCGPD ∼ RGD NPs can ensure accurate recognition and sufficient accumulation in the tumor site. After accumulation, doxorubicin (DOX) can be released from MCGPD ∼ RGD NPs in a mild acidic tumor microenvironment (TME) for highly efficient chemotherapy. Upon 808 nm laser irradiation, the overexpressed matrix metalloproteinase-2 (MMP-2) in the TME and the heat produced from the PDA coating trigger Gel NP degradation to expose chlorin e6 (Ce6) and Met from the cavity of MCGPD ∼ RGD NPs. The exposed Met elevates the O2 content and reduces ATP production in tumor sites to spur the successful O2-dependent PDT and HSP-mediated PTT. The heat generated by the PDA coating directly kills the tumor cells to ensure PTT and amplifies the chemotherapeutic effect. In vitro and in vivo assays indicate that MCGPD ∼ RGD NPs have excellent ability to promote cell apoptosis and to inhibit tumor growth. Overall, this smart responsive hydrogel nanosystem with hypoxia-relieving capacity and ATP-decreasing performance provides a promising strategy against cancer.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Chaonan Shi,Minglong Chen,Xiaodie Li,Yanping Fu,Dan Yang,Ting Wen,Wanchen Zhao,Ying Sun,Wenhao Wang,Chao Lu,Qiaoli Wu,Chuanbin Wu,Xin Pan,Guilan Quan
Immunogenic cell death (ICD) is associated with the release of damage-associated molecular patterns, including ATP, to promote an effective immune cycle against tumors. However, tumors have evolved an effective strategy for degrading extracellular immunostimulatory ATP via the ATP-adenosine axis, allowing the sequential action of the ectonucleotidases CD39 to degrade accumulated immunostimulatory ATP into pleiotropic immunosuppressive adenosine. Here, an ingenious dissolving microneedle patch (DMNs) is designed for the intralesional delivery of CD39 inhibitor (sodium polyoxotungstate, POM-1) and ICD inducer (IR780) co-encapsulated solid lipid nanoparticles (P/I SLNs) for antitumor therapy. Upon insertion into the tumor site, IR780 induces ICD modalities with the release of damage-associated molecular patterns from endogenous tissues, which activates the antitumor immune cycle. Simultaneously, POM-1 promotes the liberation of immunostimulatory ATP and lowers the level of immunosuppressive extracellular adenosine, which supported immune control of tumors via recruiting CD39-expressing immune cells. In vivo antitumor studies prove that this platform can effectively eliminate mice melanoma (tumor growth inhibitory rate of 96.5%) and colorectal adenocarcinoma (tumor growth inhibitory rate of 93.5%). Our results shed light on the immunological aspects of combinatorial phototherapy and ATP-adenosine regulation, which will broaden the scope of synergistic antitumor immunotherapy .
研究领域:
癌症免疫疗法
·
药学
·
生物医学工程
·
分子生物学
✓ 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）