JOURNAL OF MOLECULAR RECOGNITION
·
2018
·Vol. 31
·期 8
·e2714
·
IF 1.868
Juxin Yin,Jianjian Zhuang,Shaowu Lv,Ying Mu
Excessive reactive oxygen species (ROS) levels are harmful to the body. The peroxidase, GPx, and the superoxide dismutase, SOD, are important antioxidant enzymes for preventing ROS-induced damage. Se-CuZn-65P is an enzyme mimetic with dual GPx and SOD antioxidant function. However, currently, its production is mainly based on the cysteine auxotrophic expression technique, which is inefficient, expensive, and time consuming. In this study, we combined protein engineering and the chemical mutation method to synthesize Se-CuZn-65P. The DNA sequence encoding the 65 amino acid peptide with the desired sequence transformations to incorporate the SOD and the GPx catalytic sites was cloned and expressed in a soluble protein expression vector. The protein yield increased up to 152 mg/L, which is 10 times higher than in previous studies. The SOD and GPx activity of Se-CuZn-65P was high (1181 U/mg and 753 U/μmol, respectively). The binding constant of glutathione was 5.6 × 10 4 L·mol −1 , which shows that Se-CuZn-65P efficiently catalyzed hydrogen peroxide reduction by glutathione. Mitochondrial damage experiments confirmed the double protective role of the Se-CuZn-65P peptide and demonstrated functional synergy between the SOD and the GPx domains, which indicates its potential to be used in the treatment of ROS-related diseases. Our research may give a new thought to increase the yield of mimic.
研究领域:
生物化学
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分子生物学
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药理学
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生物技术
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Cong Zhang,Yangkun Xiong,Mingyang Gong,Haixia Zhao,Shan Li,Xin Chen,Xiaochuan Ye,Zhenpeng Qiu
Hyperuricemic nephropathy, a common subtype of chronic kidney disease (CKD), has become an important global public health issue and is closely related to the dramatic increase in fructose consumption. Pachymic acid, the primary active ingredient of the edible fungal herb Poria cocos, has demonstrated the protective capacity against renal injury, but its beneficial effect on hyperuricemic nephropathy remains unclear. In this study, a fructose-diet-induced hyperuricemia nephropathy mouse model was established to reveal the efficacy of pachymic acid in inhibiting hyperuricemic nephropathy the progression. Our results showed that pachymic acid restored abnormal renal function indexes and pathological manifestations such as tubular dilatation and glomerular fibrosis in fructose-fed mice. Transcriptome sequencing results showed marked alterations in glutathione metabolism and ferroptosis signaling pathways in the kidneys of fructose-fed mice after pachymic acid treatment. Mechanistically, pachymic acid activated the Nrf2/GPX-4 signaling pathway by directly binding to Nrf2 and promoting its nuclear translocation, thereby inhibiting ferroptosis, oxidative stress, and inflammatory responses in the kidneys of fructose-fed mice. Consistent results were observed in uric acid-treated HK-2 cells. Notably, both Nrf2 inhibitor ML385 and GPX-4 inhibitor RSL3 treatments reversed the protective effects of pachymic acid against renal injury by suppressing ferroptosis in vitro and in vivo. Summary, our study provides compelling evidence that pachymic acid ameliorates renal injury in fructose-fed mice by inhibiting ferroptosis through targeted activating an Nrf2/GPX-4 pathway, suggesting that dietary supplementation with Poria cocos or pachymic acid might be an effective strategy for CKD prevention, particularly in the subtype of fructose-diet-driven hyperuricemic nephropathy.
研究领域:
药理学
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肾脏病学
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生物化学
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分子生物学
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营养学
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药物化学
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产品关联
DOI
PubMed
高影响因子
Soft Matter
·
2015
·Vol. 12
·期 4
·1192-1199
·
IF 4.029
Huixin Zou,Hongcheng Sun,Liang Wang,Linlu Zhao,Jiaxi Li,Zeyuan Dong,Quan Luo,Jiayun Xu,Junqiu Liu
Glutathione peroxidase (GPx) is a major defense against hydroperoxides as a kind of seleno-enzyme that protects cells from oxidative damage. A supramolecular vesicle with controllable GPx activity and morphology has been successfully constructed by the self-assembly of supra-amphiphiles formed by host–guest recognition between cyclodextrin and adamantane derivatives. By introducing thermosensitive poly(N-isopropylacrylamide) (PNIPAM) scaffolds and the catalytic moiety selenium into adamantane and cyclodextrin, respectively, the complex of catalysis-functionalized cyclodextrin with thermosensitivity-functionalized adamantane directed the formation of a supramolecular vesicle which acted as a GPx mimic at 37 °C. The self-assembled nanoenzyme exhibited an obvious temperature responsive characteristic and high GPx-like catalytic activity promoting the reduction of hydrogen peroxide (H2O2) with glutathione (GSH) as the reducing substrate at 37 °C. However, the vesicle disassembled when the temperature decreased to 25 °C due to the transition of PNIPAM between the coil and the globule. Interestingly, the catalytic activity changed along with the transformation of morphologies. The vesicle structure self-assembled at 37 °C provided the favorable microenvironment for the enzymatic reaction, hence we successfully developed a temperature-responsive nanoenzyme model. Moreover, the catalytic activity of the thermosensitive GPx mimic exhibited excellent reversibility and typical saturation kinetics behaviour similar to a natural enzyme catalyst. It is assumed that the proposed GPx model not only has remarkable advantages such as easy functionalization and facile preparation but also provided a new way to develop intelligent responsive materials.
研究领域:
生物化学
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材料科学
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仿生学
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DOI
PubMed
高影响因子
Soft Matter
·
2014
·Vol. 10
·期 48
·9695-9701
·
IF 4.151
Zupeng Huang,Quan Luo,Shuwen Guan,Jianxiong Gao,Yongguo Wang,Bo Zhang,Liang Wang,Jiayun Xu,Zeyuan Dong,Junqiu Liu
Artificial enzymes capable of achieving tunable catalytic activity through stimuli control of enzymatic structure transition are of significance in biosensor and biomedicine research. Herein we report a novel smart glutathione peroxidise (GPx) mimic with modulatory catalytic activity based on redox-induced supramolecular self-assembly. First, an amphiphilic Fmoc-phenylalanine-based selenide was designed and synthesized, which can self-assemble into nanospheres (NSs) in aqueous solution. The NSs demonstrate extremely low GPx activity. Upon the oxidation of hydroperoxides (ROOH), the selenide can be quickly transformed into the selenoxide form. The change of the molecular structure induces complete morphology transition of the self-assemblies from NSs to nanotubes (NTs), resulting in great enhancement in the GPx catalytic activity. Under the reduction of GSH, the selenoxide can be further reversibly reduced back into the selenide; therefore the reversible switch between the NSs and NTs can be successfully accomplished. The relationship between the catalytic activity and enzymatic structure was also investigated. The dual response nature makes this mimic play roles of both a sensor and a GPx enzyme at the same time, which can auto-detect the signal of ROOH and then auto-change its activity to achieve quick or slow/no scavenging of ROOH. The dynamic balance of ROOH is vital in organisms, in which an appropriate amount of ROOH does benefit to the metabolism, whereas surplus ROOH can cause oxidative damage of the cell instead and this smart mimic is of remarkable significance. We expect that such a mimic can be developed into an effective antioxidant drug and provide a new platform for the construction of intelligent artificial enzymes with multiple desirable properties.
研究领域:
生物化学
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仿生材料
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医学
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产品关联
DOI
PubMed
高影响因子
MATERIALS CHEMISTRY AND PHYSICS
·
2023
·
IF 4.6
Qiancun Wang,Chuanmei Zang,Yau Kei Chan,Song Wang,Weizhong Yang,Yi Deng,Tingting Zhu,Miaomiao He
Polyetheretherketone (PEEK), as a promising alternative for hard tissue implant, still has limitations in anti-pathogens for coping with the clinical challenge. To reverse this situation, CoFe 2 O 4 /MXene nanosheets modified hydrogel was spin-coated on PEEK mediated by polydopamine to endow PEEK with favorable anti-bacterial activity. The modified PEEK implant exhibits the property of photothermal therapy (PTT) for local heat, photodynamic therapy (PDT), and chemodynamic therapy (CDT) for reactive oxygen species (ROS) accumulation to realize robust anti-pathogens. The antibacterial effect can be further enhanced by glutathione (GSH) consumption owing to the glutathione peroxides (GPx)-mimetic activity of CM2. In addition, we investigated the specific effects of the designed materials on bacteria, and the experimental results showed that constructed CM2 can lead to the DNA and protein of bacterial leakage and ATP synthesis decreased, ultimately eliminating more than 99% of bacteria. Furthermore, the sample exhibits favorable blood and cell compatibility with broad prospects in clinical application. Overall, a hydrogel coating-PEEK system with robust antibacterial properties has been manufactured in our work, which can not only exhibit compatibility, but also effectively avoid implant-related infection, which shows great promise for infectious bone defect repairment.
研究领域:
材料科学
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生物材料
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生物医学工程
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纳米技术
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骨科
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DOI
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Xiaoqin Zhang,Jiale Mao,Lu Shao,Shuang Liu,Jiwang Zhou,Mingrong Mei,Zunjing Zhang
Background: Melastoma dodecandrum Lour. (MD), a traditional botanical drug known for its hypoglycemic, antioxidant, and anti-inflammatory properties, is commonly used to treat diabetes, osteoarthritis, and osteoporosis. However, its specific active components against diabetic osteoporosis remain unclear.Purpose: This study aimed to identify the key active components in MD using cell membrane chromatography coupled with mass spectrometry and validate their effects in vitro.Methods: An AGEs-induced osteoblast injury model was established. MTT assays measured cell viability, and ALP activity was assessed using a biochemical kit. Western blotting was employed to detect the expression levels of osteoblast-related proteins OCN and RUNX2 and the AGE receptor protein RAGE. ELISA was used to determine the levels of SOD, MDA, CAT, and GPx. PCR quantified TNF-α expression to evaluate the protective effects and potential mechanisms of MD. The AGEs-induced osteoblast cell membrane chromatography-mass spectrometry method facilitated the rapid identification of potentially active compounds based on their affinity for the osteoblast cell membrane. Cell experiments further validated the activity of the characteristic component isovitexin.Results: MD significantly improved cell viability in AGEs-damaged osteoblasts, enhanced ALP, SOD, CAT, and GPx activities, reduced MDA levels, increased OCN and RUNX2 protein expression, and decreased TNF-α mRNA and RAGE protein expression. Cell membrane chromatography identified 20 chemical constituents, including 13 flavonoids, 4 organic acids, 1 phenylpropanoids, 1 terpenoids, and 1 alkaloid. Cell experiments have confirmed that isovitexin has significant protective activity against osteoblasts and can inhibit the expression of specific receptor RAGE on the osteoblast membrane, consistent with the effect of MD.Conclusion: MD and its active component, isovitexin, provide protective effects against AGEs-induced osteoblast injury, offering a basis for subsequent drug development.
研究领域:
药理学
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生物化学
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细胞生物学
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分析化学
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产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2013
·Vol. 13
·期 6
·808-816
·
IF 3.742
Yuzhou Gao,Chunxi Hou,Lipeng Zhou,Dongmei Zhang,Chunqiu Zhang,Lu Miao,Liang Wang,Zeyuan Dong,Quan Luo,Junqiu Liu
An antioxidant microgel with both glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities is reported. Using computational design and genetic engineering methods, the main catalytic components of GPx are fabricated onto the surface of ferritin. The resulting seleno-ferritin (Se-Fn) monomers can self-assemble into nanocomposites that exhibit remarkable GPx activity due to the well organized multi-GPx catalytic centers. Subsequently, a porphyrin derivative is synthesized as an SOD mimic, and is employed to construct a synergistic dual enzyme system by crosslinking Se-Fn nanocomposites into a microgel. Significantly, this dual enzyme microgel is demonstrated to display better antioxidant ability than single GPx or SOD mimics in protecting cells from oxidative damage.
研究领域:
生物工程
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材料科学
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生物催化
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基因工程
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DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Zhen Rong,Zhi-Hao Ding,Yue-Hong Wu,Xue-Wei Xu
Low-density polyethylene (LDPE), which accounts for 20% of the global plastic production, is discharged in great quantities into the ocean, threatening marine life and ecosystems. Marine microorganisms have previously been reported to degrade LDPE plastics; however, the exploration of strains and enzymes that degrade LDPE is still limited. Here, an LDPE-degrading bacterium was isolated from seawater of the Changjiang Estuary, China and identified as Rhodococcus sp. C-2, the relative abundance of which was dramatically enhanced during PE-degrading microbial enrichment. The strain C-2 exhibited the degradation of LDPE films, leading to their morphological deterioration, reduced hydrophobicity and tensile strength, weight loss, as well as the formation of oxygen-containing functional groups in short-chain products. Sixteen bacterial enzymes potentially involved in LDPE degradation were screened using genomic, transcriptomic, and degradation product analyses. Thereinto, the glutathione peroxidase GPx with exposed active sites catalyzed the LDPE depolymerization with the cooperation of its dissociated superoxide anion radicals. Furthermore, an LDPE degradation model involving multiple enzymes was proposed. The present study identifies a novel PE-degrading enzyme (PEase) for polyethylene bioremediation and promotes the understanding of LDPE degradation.
研究领域:
环境科学
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微生物学
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生物技术
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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
·
2020
·Vol. 8
·期 37
·8634-8643
·
IF 5.344
Yongmei Li,Yuemei Li,Yandong Bai,Laixiang Lin,Yina Sun
Cerium oxide nanoparticles (NPs) due to their advanced catalytic performance have been widely used to treat oxidative damage. However, Ce2O3 NPs have not been further investigated in the treatment of acute oxidative injury in vivo. It is meaningful to improve the efficiency for treatment of acute oxidative injury with NPs in vivo. In this report, we designed Er3+-doped Ce2O3 (Er/Ce2O3) NPs with a size of 7.9 nm, which were used to treat acute liver injury. Er/Ce2O3 NPs realized high-efficiency catalysis of hydrogen peroxide (H2O2) at room temperature. An acute liver damage model was established through intraperitoneal injection of lipopolysaccharide (LPS) in C57 mice. By analyzing histopathological and biochemical indexes, Er/Ce2O3 NPs showed a significant improvement in LPS-induced acute liver injury. Acute liver oxidative damage can be treated within 24 hours, which proved the high catalytic efficiency of Er/Ce2O3 NPs in vivo. The activities of SOD, GPx and CTA increased and production of ROS decreased with Er/Ce2O3 NP treatment in comparison with LPS-induced injury, indicating that the mechanism of Er/Ce2O3 NPs in the treatment of acute oxidative damage of liver was mainly via catalysis of ROS products. Moreover, the protein expression levels of TNF-α, CD45 and IL-1β in liver decreased in the Er/Ce2O3 NPs-treated group, which indicated that Er/Ce2O3 NPs have the function of anti-inflammation property. Therefore, Er/Ce2O3 NPs can be applied to treat and prevent diseases caused by acute oxidative damage.
研究领域:
纳米技术
·
生物医学工程
·
药理学
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毒理学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Ziwei Liang,Yuhui Wang,Jiapu Wang,Tao Xu,Shilong Ma,Qi Liu,Liqin Zhao,Yan Wei,Xiaojie Lian,Di Huang
Ferroptosis is a novel form of regulated cell death induced by iron-dependent lipid peroxidation imbalance. It has emerged as a promising antitumor therapeutic strategy in recent years. In this work, we successfully synthesized a complex magnetic nanocube Fe 3 O 4 modified with PEI and HA by the thermal decomposition method. While loading a ferroptosis inducer RSL3 inhibited cancer cells through the ferroptosis signal transduction pathway. The drug delivery system could actively target tumor cells through an external magnetic field and HA-CD44 binding. Zeta potential analysis showed that Fe 3 O 4 [email protected] nanoparticles were more stable and uniformly dispersed in tumor acidic environment. Moreover, cellular experiments demonstrated that Fe 3 O 4 [email protected] nanoparticles could significantly inhibit the proliferation of hepatoma cells without a cytotoxic effect on normal hepatic cells. In addition, Fe 3 O 4 [email protected] played a vital role in ferroptosis by accelerating ROS production. The expression of ferroptosis-related genes Lactoferrin, FACL 4, GPX 4 and Ferritin was significantly suppressed with increasing treatment of Fe 3 O 4 [email protected] nanocubes. Therefore, this ferroptosis nanomaterial has great potential in Hepatocellular carcinoma (HCC) therapy.
研究领域:
纳米技术
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癌症生物学
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药学
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分子生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Di Liu,Si Sun,Huanhuan Qiao,Qi Xin,Sufei Zhou,Lingxia Li,Nan Song,Lijie Zhang,Qi Chen,Fangzhen Tian,Xiaoyu Mu,Shaofang Zhang,Jing Zhang,Meili Guo,Hao Wang,Xiao-Dong Zhang,Ruiping Zhang
Artificial enzymes, especially nanozymes, have attracted wide attention due to their controlled catalytic activity, selectivity, and stability. The rising Cerium-based nanozymes exhibit unique SOD-like activity, and Vanadium-based nanozymes always hold excellent GPx-like activity. However, most inflammatory diseases involve polymerase biocatalytic processes that require multi-enzyme activities. The nanocomposite can fulfill multi-enzymatic activity simultaneously, but large nanoparticles (>10 nm) cannot be excreted rapidly, leading to biosafety challenges. Herein, atomically precise Ce 12 V 6 clusters with a size of 2.19 nm are constructed. The Ce 12 V 6 clusters show excellent glutathione peroxidase (GPx) -like activity with a significantly lower Michaelis-Menten constant (K m , 0.0125 mM versus 0.03 mM of natural counterpart) and good activities mimic superoxide dismutase (SOD) and peroxidase (POD). The Ce 12 V 6 clusters exhibit the ability to scavenge the ROS including O 2 ·− and H 2 O 2 via the cascade reactions of multi-enzymatic activities. Further, the Ce 12 V 6 clusters modulate the proinflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) and consequently rescue the multi-organ failure in the lipopolysaccharide (LPS)-induced sepsis mouse model. With excellent biocompatibility, the Ce 12 V 6 clusters show promise in the treatment of sepsis.
研究领域:
纳米技术
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生物化学
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药理学
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免疫学
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医学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Na Li,Jing Tang,Congxiao Wang,Minghui Wang,Guodong Chen,Lei Jiao,Qinglai Yang,Xiaofeng Tan
The rational design of nanozymes with highly efficient reactive oxygen species (ROS) generation to overcome the resistant infection microenvironment still faces a significant challenge. Herein, the highly active Fe single-atom nanozymes (Fe SAzymes) with a hierarchically porous nanostructure were prepared through a colloidal silica-induced template method. The proposed Fe SAzymes with satisfactory oxidase (OD)-like and peroxidase (POD)-like activity can transform O 2 and H 2 O 2 to superoxide anion free radical (•O 2 - ) and hydroxyl radical (•OH), which possess an excellent bactericidal effect. Also, the glutathione peroxidase (GPX)-like activity of Fe SAzymes can consume glutathione in the infection microenvironment, thus facilitating ROS generation to enhance the sterilization effect. Besides, the intrinsic photothermal effect of Fe SAzymes further significantly boosts the enzyme-like activity to generate much more reactive oxygen species for efficient antibacterial therapy. Accordingly, both in vitro and in vivo results indicate that the Fe SAzymes with synergistically photothermal-catalytic performances exhibit satisfactory antibacterial effects and biocompatibility. This work provides new insights into designing highly efficient SAzymes for effective sterilization applications by an amount of ROS generation.
研究领域:
纳米技术
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材料科学
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生物医学工程
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微生物学
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产品关联
DOI
PubMed
高影响因子
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