ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2018
·Vol. 50
·期 6
·547-554
·
IF 2.224
Jia Qian,Lin Yun,Gou Xuejing,He Lei,Shen Dong,Chen Dongni,Xie Wei,Lu Yongjun
The gram-negative bacterium Legionella pneumophila invades human’s lung and causes Legionnaires’ disease. To benefit its survival and replication in cellular milieu, L. pneumophila secrets at least 330 effector proteins into host cells. We found that the effector WipA has the protein tyrosine phosphatase (PTP) activity but does not depend on the classical CX5R motif for activity, suggesting that WipA is an unconventional PTP. Meanwhile, the presence of three other highly conserved motifs typically seen in protein serine/threonine phosphatases and the poor inhibition of WipA activity by okadaic acid led us to propose that WipA is a bacterial protein phosphatase. In addition, the determination of the 2.55-Å crystal structure of WipA revealed that WipA resembles cold-active protein tyrosine phosphatase (CAPTPase), and therefore very likely shares the same catalytic mechanism.
研究领域:
微生物学
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分子生物学
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传染病学
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结构生物学
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产品关联
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
Food Bioscience
·
2024
·
IF 4.8
Shuze Ren,Songming Li,Mahmoud Abou-Elsoud,Rui Cui,Xing Fu,Xi Huang
Phosvitin phosphopeptides (PPP) have a high ability to chelate mineral ions and promote calcium absorption. In this study, The Fe 3 O 4 nanospheres were first synthesized by hydrothermal method, then the three magnetic nanoparticles (Fe 3 O 4 @PDA@PMAA@PAMAM, Fe 3 O 4 @PDA@Ce 4+ , and Fe 3 O 4 @PDA@TiO 2 ) were obtained by layer modification on their surfaces, respectively. The magnetic nanoparticles were characterized by TEM, XRD, VSM, and Zeta potential. TEM analysis revealed that the nanoparticles were spherical and regular in shape. XRD diffraction analysis showed that the modified nanoparticles have a complete crystal structure. Meanwhile, PAMAM, Ce 4+ , TiO 2 , and other groups have been successfully modified on the nanoparticles. VSM hysteresis regression line results revealed that the magnetic nanoparticles are superparamagnetic. The three kinds of magnetic nanoparticles still maintained excellent enrichment performance after five times of repeated use. Fe 3 O 4 @PDA@TiO 2 has the best enrichment performance (167 mg g −1 ). The N/P ratio of the enriched PPP decreased from 1.36 to 0.98, which also showed that it had excellent PPP enrichment performance. Therefore, the modified magnetic nanoparticles could be an optimal PPP enrichment and purification material.
研究领域:
材料科学
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纳米技术
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生物化学
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产品关联
DOI
高影响因子
Food Bioscience
·
2022
·
IF 5.318
Ping Yan,Jiang-lan Yuan,Xu Kang,Jin-ying Lv,Xiao-cui Liu
High internal phase emulsions (HIPEs) stabilized by nanoparticles based on biomacromolecules are challenging issues in recent decade. Herein, a newly developed HIPE was investigated by using heat-denatured porcine plasma protein (PPP) nanoparticles at pH 6.5 as emulsifier, and its emulsifying stability could be significantly enhanced by compounding carrageenan (CG). In the miscible system, PPP and CG formed hybrid particles through non-covalent interaction, and the sizes and zeta-potentials of the particles increased significantly along with addition of CG (from 0 to 0.7%, w/v), reached up to about 3.6 μm and −53 mV at 0.5% (w/v), respectively. CG weakened the ability of PPP to lower interfacial tension of oil/water (O/W), but increased the apparent viscosity of the system. The results from CLSM , rheology and stability experiments indicated a significant increasing trend of the HIPEs stability and solid-like characteristics along with addition of CG. Compared with the controls including bovine serum albumin (BSA), BSA-CG and CG alone, PPP-CG hybrid particles had good performance in fabricating and stabilizing the HIPEs. The work revealed the novel function of PPP as emulsifier of HIPEs and so offered the theoretical direction for application of PPP as a mass by-product, as well as an excellent HIPEs system for food , medicine and cosmetics fields.
研究领域:
食品科学
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生物材料
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化学工程
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产品关联
DOI
高影响因子
ACS Omega
·
2025
·
IF 4.3
Chaofan Deng,Chun Cai
Pd–Cu bimetallic catalysts were successfully synthesized for the dehydrogenation of Bisphenol Z (BPZ) by an impregnation-reduction method. The obtained catalyst was studied by XRD, HRTEM, XPS, BET, and NH3-TPD techniques and effectively applied in the highly selective cleavage dehydrogenation of BPZ to give PPP > 99% yield at 270 °C and atmospheric pressure in the solvent-free condition. It was demonstrated that the “synergistic effect” of the bimetallic catalysts could effectively promote the cleavage dehydrogenation reaction. Pd species served as the primary active sites for the adsorption and dissociation of H* and the activation of C–H bonds, while the introduced Cu species accelerated the breaking process of the C–H bond. This catalyst demonstrated remarkable stability and could be reused over ten cycles without obvious decrease both in yield and selectivity. The likely reaction pathway was outlined to elucidate the cleavage dehydrogenation mechanism according to experimental results.
研究领域:
催化化学
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化学合成
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材料科学
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有机化学
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反应机理
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2022
·Vol. 57
·期 7
·4754-4770
·
IF 4.682
Zhuang Yi,Kan Zhaojun,Jiang Yulin,He Miaomiao,Zhang Yuanyuan,Sun Xiaodong,Du Meixuan,Wang Jing,Li Yubao,Li Yunfeng,Zhang Li
In this study, we prepared a drug-laden graphene-incorporated calcium alginate (GCA) microspheres, which were then blended with the typically thermosensitive hydrogel named poly (d,l-lactide-co-glycolide)-poly (ethylene glycol)-poly (d,l-lactide-co-glycolide) triblock copolymer (PLGA-PEG-PLGA, PPP for short) to obtain an on-demand drug controlled release system triggered by near-infrared (NIR) laser, thus achieving minimally invasive treatment of tumorous defect through the in-situ curing of the GCA/PPP hydrogel after injection into the target site. The results indicate that all these drug-laden GCA/PPP hydrogels are injectable, enabling the minimally invasive treatment of defects with complex geometries and shapes. The 2%GCA/PPP could be heated up to 45.3 ºC within 3 min under NIR irradiation and showed a unique heating plateau in the heating curve, performing the desired photothermal stability and heating-up effect in comparison with the other groups. By turning on or off the NIR irradiation, GCA/PPP hydrogels could exhibit the step-shaped drug release curves, meaning that on-demand controlling the drug release is feasible by using NIR laser as the trigger. The in vitro biological assessments showed that the drug-laden GCA/PPP hydrogels were biocompatible as well as enhanced anti-tumor capability under NIR exposure, demonstrating their promise in treatment of tumorous defects with irregular shapes.
研究领域:
生物医学工程
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材料科学
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肿瘤学
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产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·Vol. 24
·期 1
·914
·
IF 15
Li Chenhao,Zhang Chao,Zhang Chuanqi,Duan Shiyu,Zhang Jiali,Wang Hongyue
AKI-to-CKD progression is shaped by sustained tubular stress, ferroptosis-related iron imbalance, and oxidative injury. To target this process, we developed an MHY1485-loaded molybdenum oxide (MoOx) nanozyme coated with a pH-responsive phenylboronic acid-polyethylene glycol-phenylboronic acid (PBA-PEG-PBA) polymer (MHY@MO@PPP). We tested whether this platform could weaken the ferroptosis-associated injury loop and delay AKI-to-CKD transition through regulation of the Fe 2+ -mechanistic target of rapamycin complex 1 (mTORC1)-glutathione peroxidase 4 (GPX4) axis. Material properties were examined by dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Biological activity was assessed in erastin-induced ferroptotic human renal proximal tubular epithelial (HK-2) cells and in a C57BL/6 mouse unilateral ischemia-reperfusion injury (UIRI) model. MHY@MO@PPP showed stimulus-responsive MHY1485 release under simulated lesion-like conditions, lowered reactive oxygen species (ROS), lipid peroxidation, and free Fe 2+ , restored mitochondrial function, and improved cell survival. Mechanistic assays showed increased p-mTOR and GPX4 expression with reduced autophagy-related stress, supporting attenuation of the ferroptosis-related feedback state. Proteomic analysis and functional intervention experiments further implicated the Fe 2+ -mTORC1-GPX4 axis in the protective response. In vivo, MHY@MO@PPP improved renal function and reduced renal tissue injury and fibrosis. These findings support a nanozyme-based strategy that combines catalytic redox regulation with pathway modulation to mitigate AKI-to-CKD progression. Graphical abstract
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DOI
高影响因子
FOOD CHEMISTRY
·
2022
·
IF 9.231
Lihong He,Can Zeng,Lingfeng Wei,Li Xu,Fenglin Song,Jianrong Huang,Nanjing Zhong
This study aims to fabricate immobilized lipases for efficient preparation of 1,3-dioleoyl-2-palmitoyl-glycerol (OPO) through acidolysis of glycerol tripalmitate (PPP). Twelve (three types) supports and five lipases were studied carefully. Among them, the immobilized Thermomyces lanuginosa lipase (TLL) samples exhibited overall better performance than that of other immobilized lipases. Particularly, organic groups functionalized SBA-15 (R-SBA-15) supported TLL (TLL@R-SBA-15) samples gave PPP conversion from 97.70 to 99.00 % and OPO content from 59.52 to 64.73 %. After optimization, PPP conversion up to 99.07 %, OPO content 73.15 % and sn -2 palmitic acid content 90.09 % were obtained with TLL@C 18 H 37 -SBA-15 as catalyst. Moreover, TLL@C 18 H 37 -SBA-15 exhibited better acidolysis performance from 50 °C than that from 60 to 80 °C, which helped inhibit acyl migration. In addition, after 5 cycles of reuse, TLL@C 18 H 37 -SBA-15 retained 81.04 % (based on OPO content) and 98.88 % (based on sn- 2 palmitic acid content) of its initial activity, indicating it had an attractive prospect in future applications.
研究领域:
生物化学
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生物技术
·
催化
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Congjun Xu,Haolan Yang,Zhanghong Xiao,Tao Zhang,Zilin Guan,Jie Chen,Hualu Lai,Xiaoyu Xu,Yanjuan Huang,Zeqian Huang,Chunshun Zhao
The pentose phosphate pathway (PPP) plays a critical role by providing ribulose-5-phosphate (Ru5P) and NADPH for nucleotide synthesis and reduction energy, respectively. Accordingly, blocking the PPP process may be an effective strategy for enhancing oxidation therapy and inhibiting cell replication. Here, we designed a novel reduction-responsive PEGylated prodrug and constructed nanoparticles [email protected] to simultaneously deliver a PPP blocker, dehydroepiandrosterone (DHEA), and chemotherapeutic camptothecin (CPT) to integrate amplification of oxidation therapy and enhance cell replication inhibition. Following cellular uptake, DHEA and CPT were released from [email protected] in the presence of high glutathione (GSH) levels. As expected, DHEA-mediated reduction level decreases and CPT-induced oxidation level increases synergistically, breaking the redox balance to aggravate cancer oxidative stress. In addition, suppressing nucleotide synthesis by DHEA through the reduction of Ru5P and blocking DNA replication by CPT further motivates a synergistic inhibition effect on tumor cell proliferation . The results showed that [email protected] featuring multimodal treatment has satisfactory antitumor activity both in vitro and in vivo . This study provides a new tumor treatment strategy, which combines the amplification of oxidative stress and enhancement of inhibition of cell proliferation based on inhibition of the PPP process.
研究领域:
药理学
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肿瘤学
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纳米技术
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生物化学
·
治疗学
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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）