Small
·
2023
·
IF 13.3
Zhiyan Li,Xianghui Li,Yanjun Lu,Xudong Zhu,Wenxuan Zheng,Kai Chen,Song Liu,Jinhui Wu,Wenxian Guan
Photodynamic therapy (PDT) has promising applications. However, the lethal function of reactive oxygen species (ROS) produced during PDT is typically limited. This restriction is induced by oxygen shortage in the tumor microenvironment due to tumor cell hypermetabolism and reductive chemicals overexpression in tumor tissues. Glutamine (Gln) metabolism is crucial for malignancy development and is closely associated with redox. Herein, a novel nanoparticle (NP) named IRCB@M is constructed to boost PDT through dual effects. This NP simultaneously blocks aerobic respiration and inhibits cellular reduced substances by blocking the Gln metabolic pathway. Within the nanocomplex, a photosensitizer (IR-780) and a glutaminase inhibitor (CB-839) are self-assembled and then encapsulated by cancer cell membranes for homologous targeting. The Gln metabolism intervention relieves hypoxia and decreases the levels of nicotinamide adenine dinucleotide phosphate (NADPH) as well as reduced glutathione (GSH) in vitro and in vivo, which are the dual amplification effects on the IR-780-mediated lethal PDT. The antitumor effects against gastric cancer are ultimately evoked in vivo, thus offering a novel concept for enhancing PDT and other ROS-dependent therapeutic approaches.
研究领域:
癌症研究
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纳米技术
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治疗学
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生物化学
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DOI
PubMed
高影响因子
Cell and Bioscience
·
2024
·Vol. 14
·期 1
·1-18
·
IF 6.1
Maimaiti Yasenjiang,Su Ting,Zhang Zhanying,Ma Lingling,Zhang Yuan,Xu Hong
This study investigates NADPH oxidase 4 (NOX4) involvement in iron-mediated astrocyte cell death in Alzheimer’s Disease (AD) using single-cell sequencing data and transcriptomes. We analyzed AD single-cell RNA sequencing data, identified astrocyte marker genes, and explored biological processes in astrocytes. We integrated AD-related chip data with ferroptosis-related genes, highlighting NOX4. We validated NOX4’s role in ferroptosis and AD in vitro and in vivo. Astrocyte marker genes were enriched in AD, emphasizing their role. NOX4 emerged as a crucial player in astrocytic ferroptosis in AD. Silencing NOX4 mitigated ferroptosis, improved cognition, reduced Aβ and p-Tau levels, and alleviated mitochondrial abnormalities. NOX4 promotes astrocytic ferroptosis, underscoring its significance in AD progression.
研究领域:
神经科学
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分子生物学
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基因组学
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神经退行性疾病
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DOI
PubMed
高影响因子
Biotechnology Journal
·
2025
·Vol. 20
·期 8
·e70090
·
IF 3.1
Hailing Dai,Guoqiang Chen,Jingjiu Mu,Afreen Shagufta,Lijuan Liu,Fan Wang,Sheng Dong,Xiao Men,Lei Wang,Haibo Zhang
Enzymatic biofuel cells face substrate limitations due to enzyme specificity of the electrode. A universal electrode was designed by immobilizing ferredoxin-NADP + oxidoreductase (FNR) with bacterial cellulose (BC), carbon nanotubes (CNTs), and silver nanowires (AgNWs). The electrode coupled with NADPH-dependent malic enzyme or glucose dehydrogenase generated electricity using malic acid and glucose, respectively. The open-circuit voltage reached 79.36 and 75.8 mV, respectively, and the accumulation of pyruvate and gluconate reached 0.30 and 0.25 mM, respectively, after 12 h. This strategy enables electron transfer from diverse substrates via NADPH.
研究领域:
生物燃料电池
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酶催化
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电化学
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纳米材料
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能量转换
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生物技术
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DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2021
·
IF 5.221
Jia Hao-Yu,Yang Zi-Yue,Chen Qi,Zong Min-Hua,Li Ning
Catalytic promiscuity is a promising starting point for improving the existing enzymes and even creating novel enzymes. In this work, site-directed mutagenesis was performed to improve promiscuous alcohol dehydrogenase activity of reductive aminase from Aspergillus oryzae (AspRedAm). AspRedAm showed the cofactor preference toward NADPH in reductive aminations, while it favored NADH in the reduction reactions. Some key amino acid residues such as N93, I118, M119, and D169 were identified for mutagenesis by molecular docking. Variant N93A showed the optimal pH and temperature of 8 and 30°C, respectively, in the reduction of 5-hydroxymethylfurfural (HMF). The thermostability was enhanced upon mutation of N93 to alanine. The catalytic efficiency of variant N93A (kcat/Km, 23.6 mM−1 s−1) was approximately 2-fold higher compared to that of the wild-type (WT) enzyme (13.1 mM−1 s−1). The improved catalytic efficiency of this variant may be attributed to the reduced steric hindrance that stems from the smaller side chain of alanine in the substrate-binding pocket. Both the WT enzyme and variant N93A had broad substrate specificity. Escherichia coli (E. coli) cells harboring plain vector enabled selective reduction of biobased furans to target alcohols, with the conversions of 35–95% and the selectivities of >93%. The introduction of variant N93A to E. coli resulted in improved substrate conversions (>98%) and selectivities (>99%).
研究领域:
生物化学
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酶学
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生物催化
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代谢工程
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2021
·
IF 5.858
Mingming Sun,Hao Sheng,Tingfeng Wu,Jiaqi Song,Huanran Sun,Yingzhi Wang,Jiyan Wang,Zhen Li,Huifang Zhao,Junzhen Tan,Yanping Li,Guo Chen,Qingrong Huang,Yuan Zhang,Bei Lan,Shuangping Liu,Changliang Shan,Shuai Zhang
Reprogramming of energy metabolism is a hallmark of cancer, and the pentose phosphate pathway (PPP) is a major glucose metabolic pathway important for meeting the cellular demands of biosynthesis and anti-oxidant defense. Our previous study showed that phosphoinositide 3-kinase enhancer-activating Akt (PIKE-A) plays an important role in glioblastoma cell survival and growth under cellular energy stress condition. However, the crucial functions of PIKE-A in cancer energy metabolism are poorly understood. In the present study, we show that PIKE-A promotes DNA biosynthesis, NADPH production and inhibits reactive oxygen species (ROS) production, leading to increasing proliferation and growth of glioblastoma cell and suppressing cellular senescence. Mechanistically, PIKE-A binds to STAT3 and stimulates its phosphorylation mediated by tyrosine kinase Fyn , which enhances transcription of the rate-limitting enzyme glucose-6-phosphate dehydrogenase (G6PD) in the PPP. Finally, targeting PIKE-A-G6PD axis sensitizes glioblastoma to temozolomide (TMZ) treatment. This study reveals that STAT3 is a novel binding partner of PIKE-A which recruits Fyn to phosphorylate STAT3, contributing to the expression of G6PD, leading to promoting tumor growth and suppressing cellular senescence. Thus, the PIKE-A/STAT3/G6PD axis strongly links the PPP to carcinogenesis and may become a promising cancer therapeutic target.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Bioresources and Bioprocessing
·
2022
·Vol. 9
·期 1
·1-14
·
IF 4.983
Hu Qiongyue,Zhang Tanglei,Yu Hongwei,Ye Lidan
The vitamin A component retinol has become an increasingly sought-after cosmetic ingredient. In previous efforts for microbial biosynthesis of vitamin A, a mixture of retinoids was produced. In order to efficiently produce retinol at high purity, the precursor and NADPH supply was first enhanced to improve retinoids accumulation in the S. cerevisiae strain constructed from a β-carotene producer by introducing β-carotene 15,15ʹ-dioxygenase, following by screening of heterologous and endogenous oxidoreductases for retinal reduction. Env9 was found as an endogenous retinal reductase and its activity was verified in vitro. By co-expressing Env9 with the E. coli ybbO , as much as 443.43 mg/L of retinol was produced at 98.76% purity in bi-phasic shake-flask culture when the antioxidant butylated hydroxytoluene was added to prevent retinoids degradation. The retinol titer reached 2479.34 mg/L in fed-batch fermentation. The success in selective biosynthesis of retinol would lay a solid foundation for its biotechnological production. Graphical Abstract
研究领域:
生物技术
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微生物学
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代谢工程
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产品关联
DOI
PubMed
高影响因子
Current Research in Food Science
·
2022
·
IF 6.269
Xuan Chen,Liufeng Zheng,Bing Zhang,Zeyuan Deng,Hongyan Li
Oxidative stress is a potential factor in the promotion of endothelial dysfunction. In this research, flavonoids (quercetin, luteolin) combined with carotenoids (lycopene, lutein), especially quercetin-lycopene combination (molar ratio 5:1), prevented the oxidative stress in HUVEC cells by reducing the reactive oxygen species (ROS) and suppressing the expression of NADPH oxidase 4 (Nox4), a major source of ROS production. RNA-seq analysis indicated quercetin-lycopene combination downregulated inflammatory genes induced by H 2 O 2 , such as IL-17 and NF-κB. The expression of NF-κB p65 was activated by H 2 O 2 but inhibited by the quercetin-lycopene combination. Moreover, the quercetin and lycopene combination promoted the thermostability of Sirtuin 1 (SIRT1) and activated SIRT1 deacetyl activity. SIRT1 inhibitor EX-527 attenuated the inhibitory effects of quercetin, lycopene, and their combination on the expression of p65, Nox4 enzyme, and ROS. Quercetin-lycopene combination could interact with SIRT1 to inhibit Nox4 and prevent endothelial oxidative stress, potentially contributing to the prevention of cardiovascular disease.
研究领域:
药理学
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分子生物学
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细胞生物学
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心血管研究
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2020
·
IF 14.588
Yiyuan Kang,Jia Liu,Suhan Yin,Yanping Jiang,Xiaoli Feng,Junrong Wu,Yanli Zhang,Aijie Chen,Yaqing Zhang,Longquan Shao
Neurotransmission is the basis of brain functions, and controllable neurotransmission tuning constitutes an attractive approach for interventions in a wide range of neurologic disorders and for synapse-based therapeutic treatments. Graphene-family nanomaterials (GFNs) offer promising advantages for biomedical applications, particularly in neurology. Our study suggests that reduced graphene oxide (rGO) serves as a neurotransmission modulator and reveals that the cellular oxidation of rGO plays a crucial role in this effect. We found that rGO could be oxidized via cellular reactive oxygen species (ROS), as evidenced by an increased number of oxygen-containing functional groups on the rGO surface. Cellular redox signaling, which involves NADPH oxidases and mitochondria, was initiated and subsequently intensified rGO oxidation. The study further shows that the blockage of synaptic vesicle docking and fusion induced through a disturbance of actin dynamics is the underlying mechanism through which oxidized rGO exerts depressant effects on neurotransmission. Importantly, this depressant effect could be modulated by restricting the cellular ROS levels and stabilizing the actin dynamics. Taken together, our results identify the complicated biological effects of rGO as a controlled neurotransmission modulator and can provide helpful information for the future design of graphene materials for neurobiological applications.
研究领域:
神经科学
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生物医学工程
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材料科学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Wenbin Luo,Yu Tao,Shengnan Chen,Hao Luo,Xiaoping Li,Shuang Qu,Ken Chen,Chunyu Zeng
Pulmonary ischemia/reperfusion (IR) injury is the leading cause of acute lung injury, which is mainly attributed to reactive oxygen species (ROS) induced cell injuries and apoptosis. Since rosmarinic acid (RA) has been identified as an antioxidant natural ester, this natural compound might protect against pulmonary IR injury. In this study, the mice were given RA daily (50, 75, or 100 mg/kg) by gavage for 7 days before the pulmonary IR injury. We found that hypoxemia, pulmonary edema, and serum inflammation cytokines were aggravated in pulmonary IR injury. RA pretreatment (75 and 100 mg/kg) effectively reversed these parameters, while 50 mg/kg RA pretreatment was less pronounced. Our data also indicated RA pretreatment mitigated the upregulation of pro-oxidant NADPH oxidases (NOX2 and NOX4) and the downregulation of anti-oxidant superoxide dismutases (SOD1 and SOD2) upon IR injury. In vitro studies showed RA preserved the viability of anoxia/reoxygenation (AR)-treated A549 cells (a human lung epithelial cell line), and the results showed the protective effect of RA started at 5 μM concentration, reached its maximum at 15 μM, and gradually decreased at 20-25 μM. Besides, RA pretreatment (15 μM) greatly reduced the lactate dehydrogenase release levels subjected to AR treatment. Moreover, the results of our research revealed that RA eliminated ROS production and reduced alveolar epithelial cell apoptosis through activating the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway, which was supported by using wortmannin, because in the presence of wortmannin, the RA-mediated protection was blocked. Meanwhile, wortmannin also reversed the protective effects of RA in mice. Together, our results demonstrate the beneficial role of RA in pulmonary IR injury via PI3K/Akt-mediated anti-oxidation and anti-apoptosis, which could be a promising therapeutic intervention for pulmonary IR injury.
研究领域:
药理学
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肺科学
·
细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
·
2022
·Vol. 70
·期 2
·697-706
·
IF 2.724
Shijin Wu,Bijiao Wang,Hongde Yan
Asymmetric reduction of ( R )-carvone and ketoisophorone by an engineered ene-reductase from Galdieria sulphuraria (GsOYE) combined with glucose dehydrogenase for NADPH regeneration were studied. A semi-rational protein engineering was used to enhance the activity and selectivity of GsOYE. Upon the sequence alignment and molecular docking results, two amino acid residues at positions 66 and 270 were selected as saturation mutation sites. Finally, a single substitution variant of GsOYE-N270A with complete conversion (100%) and diastereoselectivity (de p >99%) for reduction of ( R )-carvone and a double substitution variant GsOYE-Y66P/N270H with improved stereoselectivity for reduction of ketoisophorone were obtained.
研究领域:
生物化学
·
蛋白质工程
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催化
·
酶学
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产品关联
DOI
PubMed
高影响因子
PLANT JOURNAL
·
2023
·
IF 7.2
Xiangyang Li,Linru Chen,Xiaoyue Zeng,Kaixin Wu,Jiayu Huang,Mengmeng Liao,Yue Xi,Guohui Zhu,Xiuying Zeng,Xuewen Hou,Zhisheng Zhang,Xinxiang Peng
SUMMARY Sensing of environmental challenges, such as mechanical injury, by a single plant tissue results in the activation of systemic signaling, which attunes the plant's physiology and morphology for better survival and reproduction. As key signals, both calcium ions (Ca 2+ ) and hydrogen peroxide (H 2 O 2 ) interplay with each other to mediate plant systemic signaling. However, the mechanisms underlying Ca 2+ -H 2 O 2 crosstalk are not fully revealed. Our previous study showed that the interaction between glycolate oxidase and catalase, key enzymes of photorespiration, serves as a molecular switch (GC switch) to dynamically modulate photorespiratory H 2 O 2 fluctuations via metabolic channeling. In this study, we further demonstrate that local wounding induces a rapid shift of the GC switch to a more interactive state in systemic leaves, resulting in a sharp decrease in peroxisomal H 2 O 2 levels, in contrast to a simultaneous outburst of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived apoplastic H 2 O 2 . Moreover, the systemic response of the two processes depends on the transmission of Ca 2+ signaling, mediated by glutamate-receptor-like Ca 2+ channels 3.3 and 3.6. Mechanistically, by direct binding and/or indirect mediation by some potential biochemical sensors, peroxisomal Ca 2+ regulates the GC switch states in situ , leading to changes in H 2 O 2 levels. Our findings provide new insights into the functions of photorespiratory H 2 O 2 in plant systemic acclimation and an optimized systemic H 2 O 2 signaling via spatiotemporal interplay between the GC switch and NADPH oxidases.
研究领域:
植物生物学
·
分子生物学
·
细胞信号
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生物化学
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Shanshan Wei,Wanjun Ma,Chuanhao Jiang,Jiaqin Liu,Jian Liu,Bikui Zhang,Wenqun Li
Clinical application of doxorubicin (Dox) in cancer chemotherapy is limited by its cardiotoxicity. Present study aimed to demonstrate the effect and mechanism of hyperoside in Dox-induced cardiotoxicity. C57BL/6 mice were injected with 12 mg/kg of Dox, and 1 μM Dox was exposed to primary cardiomyocytes. Cardiac function was evaluated by echocardiographic and myocardial enzyme levels. Cardiomyocyts apoptosis was analyzed by TUNEL staining and flow cytometry. Network pharmacology and molecular docking were utilized to explore potential targets of hyperoside. Protein expressions were detected by western blot and enzyme activities were determined by colorimetry. Cardiac dysfunction and cardiomyocyte apoptosis induced by Dox were attenuated by hyperoside. Mechanism of hyperoside was mainly related to “oxidative stress” pathway. Hyperoside exhibited strong binding activities with nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs, the main source of ROS in cardiomyocytes) and cyclooxygenases (COXs). Experiments proved that hyperoside suppressed the ROS generation and the elevated activities of NOXs and COXs induced by Dox. Dox also triggered the activation of NLRP3 inflammasome, which was reversed by hyperoside. Hyperoside bound to NOXs and COXs, which prevents Dox-induced cardiotoxicity by inhibiting NOXs/ROS/NLRP3 inflammasome signaling pathway. Hyperoside holds promise as a therapeutic strategy for Dox-induced cardiotoxicity.
研究领域:
药理学
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心脏病学
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肿瘤学
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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）