BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Lei Wang,Yufeng Tao,Xuesong Wang,Yuhan Gan,Yuting Zeng,Shasha Li,Qing Zhu
Phellinus igniarius is an important medicinal and edible fungus with diverse biological activities. This study aimed to investigate the effects of aqueous extract from P. igniarius (API) on the treatment of hyperuricemia (HUA) and related kidney damage. The chemical constituents of API were determined. The therapeutic effects of API on HUA and renal injury were assessed in adenine/potassium oxonate (PO)-treated mice. The constituent analysis of API revealed a predominance of polysaccharides (33.4 %), followed by total flavonoids (9.1 %), and total triterpenoids (3.5 %). Compared to control, the adenine/PO treatment greatly elevated serum uric acid (UA) levels but this elevation was attenuated by API. In the liver, the expression and activity of xanthine oxidase (XOD) were increased by HUA which were diminished by API. Furthermore, API was found to enhance the expression of UA transporter ABCG2 in the kidney and intestine of HUA mice, suggesting elevating UA excretion. Additionally, API ameliorated HUA-induced renal injury, as indicated by reduced serum BUN/creatinine levels, decreased glomerular and tubular damage, and lowered fibrotic levels. Network pharmacology analysis predicted that P. igniarius may regulate mitochondrial function to improve HUA-related renal injury. This prediction was then substantialized by the API-induced upregulation of NAD+/NADH ratio, ATP level, SOD2 activity, and expression of SOD2/PCG-1α/PPARγ in the kidney of HUA mice. Our results demonstrate that API may effectively ameliorate HUA by reducing UA production in the liver and enhancing UA excretion in the kidney and intestine, and it might be a potential therapy to HUA-related renal injury.
研究领域:
药理学
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医学
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生物化学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Sizhu Ren,Ziyuan Wang,Muhammad Bilal,Yuxiao Feng,Yunhong Jiang,Shiru Jia,Jiandong Cui
Multienzymatic conversion of carbon dioxide (CO 2 ) into chemicals has been extensively studied. However, regeneration and reuse of co-factor are still the main problems for the efficient conversion of CO 2 . In this study, a nanoscale multienzyme reactor was constructed by encapsulating simultaneously carbonic anhydrase (CA), formate dehydrogenase (FateDH), co-factor (NADH), and glutamate dehydrogenases (GDH) into ZIF-8. In the multienzyme reactors, cationic polyelectrolyte (polyethyleneimine, PEI) was doped in the ZIF-8 by dissolving it in the precursors of ZIF-8. Co-factor (NADH) was anchored in ZIF-8 by ion exchange between PEI (positive charge) and co-factor (negative charge), and regenerated through GDH embedded in the ZIF-8, thus keeping high activity of FateDH. Activity recovery of FateDH in the multienzyme reactors reached 50%. Furthermore, the dissolution of CO 2 in the reaction solution was increased significantly by the combination of CA and ZIF-8. As a result, the nanoscale multienzyme reactor exhibited superior capacity for conversion of CO 2 to formate. Compared with free multienzyme system, formate yield was increased 4.6-fold by using the nanoscale multienzyme reactor. Furthermore, the nanoscale multienzyme reactor still retained 50% of its original productivity after 8 cycles, indicating excellent reusability.
研究领域:
生物技术
·
酶工程
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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
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Qiong Hu,Luofeng Su,Yilin Luo,Xiaojing Cao,Shuhan Hu,Shiqi Li,Yiyi Liang,Sijie Liu,Wanjing Xu,Dongdong Qin,Li Niu
The assay of kinase activity with ultrahigh sensitivity is important to medical diagnostics and drug discovery. Herein, we report the biologically mediated RAFT polymerization (BMRP) and its potential use as an efficient amplification strategy in the ultrasensitive electrochemical sensing of kinase activity. In BMRP, the reversible addition–fragmentation chain-transfer (RAFT) process is initiated and sustained by the reduced form of coenzyme I (i.e., NADH), which can efficiently mediate the direct fragmentation of thiocarbonylthio (TCT) compounds (or the TCT-capped dormant chains) to produce an initiating/propagating radical under mild conditions. Due to the absence of exogenous radicals, the notorious radical termination in RAFT equilibrium can be greatly suppressed. For the sensing of kinase activity, the recognition peptides, without carboxyl groups, are immobilized via the Au–S self-assembly. After phosphorylation, TCT compounds (as RAFT agents) are tethered to the enzymatically generated phosphate groups via the carboxylate-Zr(IV)-phosphate (CZP) linkage. Subsequently, the BMRP of ferrocenylmethyl methacrylate (FcMMA) results in the labeling of each phosphate group with hundreds to thousands of Fc tags, thereby greatly amplifying the sensing signal. Obviously, the BMRP-based strategy is biologically friendly, highly efficient, uncomplicated, and quite low-cost. The detection limit of 1.85 mU/mL has been achieved toward the selective sensing of the cAMP-dependent protein kinase (PKA). Moreover, the proposed kinase sensor is applicable to inhibitor screening and kinase activity sensing in serum samples. By virtue of its low cost, high sensitivity and selectivity, and uncomplicated operation, the proposed kinase sensor holds great potential in medical diagnostics and drug discovery.
研究领域:
分析化学
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生物化学
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医学诊断
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药物发现
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电化学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Jia-Yi Zheng,Xiao-Yuan Ji,An-Qi Zhao,Fang-Yuan Sun,Li-Fang Liu,Gui-Zhong Xin
Mitochondrial complex activity controls a multitude of physiological processes by regulating the cellular metabolism. Current methods for evaluating mitochondrial complex activity mainly focus on single metabolic reactions within mitochondria. These methods often require fresh samples in large quantities for mitochondria purification or intact mitochondrial membranes for real-time monitoring. Confronting these limitations, we shifted the analytical perspective toward interactive metabolic networks at the whole-cell level to reflect mitochondrial complex activity. To this end, we compiled a panel of mitochondrial respiratory chain-mapped metabolites (MRCMs), whose perturbations theoretically provide an overall reflection on mitochondrial complex activity. By introducing N-dimethyl-p-phenylenediamine and N-methyl-p-phenylenediamine as a pair of mass spectrometry probes, an ultraperformance liquid chromatography-tandem mass spectrometry method with high sensitivity (LLOQ as low as 0.2 fmol) was developed to obtain accurate quantitative data of MRCMs. Machine learning was then combined to capture the relationship between MRCMs and mitochondrial complex activity. Using Complex I as a proof-of-concept, we identified NADH, alanine, and phosphoenolpyruvate as metabolites associated with Complex I activity based on the whole-cell level. The effectiveness of using their concentrations to reflect Complex I activity was further validated in external data sets. Hence, by capturing the relationship between metabolites and mitochondrial complex activity at the whole-cell level, this study explores a novel analytical paradigm for the interrogation of mitochondrial complex activity, offering a favorable complement to existing methods particularly when sample quantities, type, and treatment timeliness pose challenges. More importantly, it shifts the focus from individual metabolic reactions within mitochondria to a more comprehensive view of an interactive metabolic network, which should serve as a promising direction for future research into the functional architecture between mitochondrial complexes and metabolites.
研究领域:
分析化学
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生物化学
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机器学习
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代谢组学
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线粒体生物学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-11
·
IF 4.259
Zhao Hongting,Li Huihui,Hao Shuangying,Chen Jiping,Wu Jing,Song Chuanhui,Zhang Meng,Qiao Tong,Li Kuanyu
Friedreich ataxia is a progressive neurodegenerative disease caused by the expansion of GAA trinucleotide repeats within the first intron of the FXN gene, which encodes frataxin. The pathophysiology of the disease is thought to be derived from the decrease of Fe-S cluster biogenesis due to frataxin deficiency. There is currently no effective treatment for the disease. In our study, we demonstrated that treatment with the mitochondrion-targeted peptide SS-31 reduced frataxin deficiency-induced oxidative stress in lymphoblasts and fibroblasts derived from patients. Interestingly, SS-31 treatment translationally upregulated the protein level of frataxin in a dose-dependent manner. Furthermore, SS-31 treatment increased the enzymatic activities of the iron-sulphur enzymes, including aconitase and complex II and III of the respiratory chain. Further evaluation of the quality of mitochondria showed that mitochondrial membrane potential, ATP content, NAD + /NADH, and the morphology of mitochondria all improved. Our results suggest that SS-31 might potentially be a new drug for the early treatment of Friedreich ataxia.
研究领域:
神经退行性疾病
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分子生物学
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线粒体生物学
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遗传病
✓ 已验证
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2019
·
IF 3.197
Zhenlong Chen,Yuhui Yang,Shumei Mi,Qingsheng Fan,Xiaoming Sun,Baichuan Deng,Guoyao Wu,Yafei Li,Quancheng Zhou,Zheng Ruan
Chlorogenic acid (CGA) is a type of phenolic acid that has antioxidant and anti-inflammatory activities. In this study, we investigated the hepatoprotective effect of CGA in lipopolysaccharide (LPS)-treated rats. Supplementation with CGA attenuated ( P < 0.05) hepatocyte necrosis and inflammatory cell infiltration, decreased ( P < 0.05) the activities of serum transaminases and alkaline phosphatase and the level of total bilirubin, and increased ( P < 0.05) the level of serum total protein in comparison with the LPS-only group. In addition, CGA potently inhibited ( P < 0.05) the LPS-induced drop in the activities of mitochondrial NADH dehydrogenase and ATP synthase and the contents of ATP and AMP in the liver. Furthermore, CGA could partially counteract the changes induced by lipopolysaccharide in many metabolic pathways, such as energy metabolism, amino acid metabolism, and glutathione metabolism. In summary, our study showed that CGA supplementation had a protective effect against LPS-induced chronic liver injury.
研究领域:
药理学
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肝病学
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免疫学
·
代谢学
✓ 已验证
DOI
高影响因子
Frontiers in Chemistry
·
2022
·
IF 5.545
Xiao Ni,Yuyan Zhang,Chuhan Xue,Xiaojun Chen
Ochratoxin A (OTA) is a harmful mycotoxin, which is mainly secreted by Penicillium and Aspergillus species. In this work, an electrochemical aptasensor is presented for OTA detection based on Au nanoparticles (AuNPs) modified zeolite imidazolate frameworks (ZIFs) ZIF-8 platform and duplex-specific nuclease (DSN) triggered hybridization chain reaction (HCR) signal amplification. G-quadruplex-hemin assembled HCR nanowire acted as a nicotinamide adenine dinucleotide (NADH) oxidase and an HRP-mimicking DNAzyme. Besides, thionine (Thi) was enriched as a redox probe for signal amplification in this pseudobienzyme electrocatalytic system. Under the optimal conditions, the analytical response ranged from 1 to 10 7 fg ml −1 with a detection limit of 0.247 fg ml −1 . Furthermore, the aptasensor was proven to be applied in real wheat samples with a recovery between 96.8 and 104.2%, illustrating the potential prospects in practical detection.
研究领域:
分析化学
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毒理学
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食品科学
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纳米技术
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电化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
WATER RESEARCH
·
2024
·
IF 11.4
Guang Yang,Yudong Luo,Yanhong Bian,Xi Chen,Lu Chen,Xia Huang
In electro-mediated biological system (EMBS), biological anode and cathode components were incorporated into an anaerobic bioreactor, providing a small amount of oxygen to the cathode as an electron acceptor. Oxygen diffusion also impacts the anode's anaerobic ecological environment. This study unraveled how oxygen influences the metabolism and electron transport chain during the biological oxidation of refractory organics. Under the influence of electromotive force, the straight-chain model pollutant N,N -dimethylformamide (DMF) showed rapid degradation and better ammonification, with maximum rates reaching 0.53 h -1 and 26.6 %, respectively. Elevated electromotive force promoted the enrichment of functional electroactive bacteria on the anode and enhanced the availability of electron storage sites, thereby facilitating electron transfer at the anode-biofilm interface. Conversely, the anodic micro-aerobic environment disrupted the anaerobic microbial community structure, and the competitive interactions among fermentative bacteria and electroactive bacteria inhibited DMF degradation. Metagenomic analysis confirmed that cathodic oxygen up-regulated the pyruvate metabolism and the tricarboxylic acid (TCA) cycle to generate NADH and synthesize ATP. The electromotive force induced by cathodic oxygen accelerated the electron transfer in respiratory chains of electroactive bacteria, driving the oxidation of NADH and enhancing the degradation of organics. This study improves our understanding of the regulatory mechanisms governing metabolic pathways under the influence of cathodic oxygen. It offers potential for developing more efficient EMBS in industrial wastewater pretreatment, ensuring that oxygen is prevented from diffusing to the anode during micro-aeration at the cathode.
研究领域:
环境工程
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生物技术
·
微生物学
·
废水处理
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Jun Cheng,Hui Li,Lingkan Ding,Junhu Zhou,Wenlu Song,Yu-You Li,Richen Lin
The efficiency of microbial electron transfer is fundamental for determining the performance of fermentative hydrogen/methane production. To facilitate microbial electron transfer, conductive magnetite nanoparticles (MNPs) were added into a cascading dark fermentation and anaerobic digestion system that was inoculated with Enterobacter aerogenes ZJU1 and methanogenic activated sludge (MAS), respectively. During the hydrogen-producing stage, the ratio of NADH/NAD + and the activities of hydrogenase and electron transport system (ETS) of E. aerogenes ZJU1 were all increased by dosing 200 mg/L MNPs, which was conducive to hydrogen production through the NADH-dependent pathway. In the presence of 200 mg/L MNPs, hydrogen production increased by 21.1%, while subsequent methane production improved by 22.9%. Electrochemical analysis demonstrated the improvement in extracellular electron transfer capacity of MAS after adding MNPs, which can be ascribed to the contribution of MNPs and electrochemically active extracellular polymeric substances (EPS) induced by MNPs, such as humic acid-like and fulvic acid-like substances. Bacteria Syntrophomonas and Archaea Methanosarcina were the dominating enriched syntrophic partners, and the expression of functional genes involved in CO 2 reduction to methane pathway was found to increase. Therefore, a more efficient fermentative hydrogen and methane co-production system was established by improving microbial electron transfer with the addition of MNPs.
研究领域:
环境工程
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微生物学
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生物技术
·
生物能源
✓ 已验证
产品关联
DOI
高影响因子
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
·
2020
·Vol. 117
·期 27
·15599-15608
·
IF 9.412
Jiayi Liu,Yifeng Wei,Lianyun Lin,Lin Teng,Jinyu Yin,Qiang Lu,Jiawei Chen,Yuchun Zheng,Yaxin Li,Runyao Xu,Weixiang Zhai,Yangping Liu,Yanhong Liu,Peng Cao,Ee Lui Ang,Huimin Zhao,Zhiguang Yuchi,Yan Zhang
2(S)-dihydroxypropanesulfonate (DHPS) is a microbial degradation product of 6-deoxy-6-sulfo-d-glucopyranose (sulfoquinovose), a component of plant sulfolipid with an estimated annual production of 1010 tons. DHPS is also at millimolar levels in highly abundant marine phytoplankton. Its degradation and sulfur recycling by microbes, thus, play important roles in the biogeochemical sulfur cycle. However, DHPS degradative pathways in the anaerobic biosphere are not well understood. Here, we report the discovery and characterization of two O2-sensitive glycyl radical enzymes that use distinct mechanisms for DHPS degradation. DHPS-sulfolyase (HpsG) in sulfate- and sulfite-reducing bacteria catalyzes C–S cleavage to release sulfite for use as a terminal electron acceptor in respiration, producing H2S. DHPS-dehydratase (HpfG), in fermenting bacteria, catalyzes C–O cleavage to generate 3-sulfopropionaldehyde, subsequently reduced by the NADH-dependent sulfopropionaldehyde reductase (HpfD). Both enzymes are present in bacteria from diverse environments including human gut, suggesting the contribution of enzymatic radical chemistry to sulfur flux in various anaerobic niches.
研究领域:
微生物学
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环境科学
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生物地球化学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2023
·Vol. 23
·期 1
·1-14
·
IF 3.9
Zhang Ke,Ji Xiawei,Song Zhengyang,Song Wenjing,Huang Qunjia,Yu Tiantian,Shi Dibang,Wang Fangyan,Xue Xiangyang,Guo Junping
Background Cervical cancer (CC) is a common gynecological malignancy with high morbidity worldwide. Butyrate, a short-chain fatty acid produced by intestinal flora, has been reported to inhibit cervical carcinogenesis. This study aimed to investigate the pro-apoptotic effects of butyrate on CC and the underlying mechanisms. Methods Human HeLa and Ca Ski cells were used in this study. Cell proliferation, cell migration and invasion were detected by CCK-8 and EdU staining, transwell and wound healing assay, respectively. Cell cycle, mitochondrial membrane potential and apoptosis were evaluated by flow cytometry. Western blot and RT-qPCR were carried out to examine the related genes and proteins to the mitochondrial complex Ι and apoptosis. Metabolite changes were analyzed by energy metabolomics and assay kits. The association between G protein-coupled receptor 41, 43, 109a and CC prognosis was analyzed using data from The Cancer Genome Atlas (TCGA). Results CCK-8 results showed significant inhibition of CC cell proliferation induced by butyrate treatment, which was confirmed by EdU staining and cell cycle detection. Data from the transwell and wound healing assay revealed that CC cell migration was dramatically reduced following butyrate treatment. Additionally, invasiveness was also decreased by butyrate. Western blot analysis showed that cleaved Caspase 3 and cleaved PARP, the enforcers of apoptosis, were increased by butyrate treatment. The results of Annexin V/PI staining and TUNEL also showed an increase in butyrate-induced apoptotic cells. Expression of Cytochrome C (Cytc), Caspase 9, Bax, but not Caspase 12 or 8, were up-regulated under butyrate exposure. Mechanistically, the decrease in mitochondrial NADH and NAD + levels after treatment with butyrate was observed by energy metabolomics and the NAD+/NADH Assay Kit, similar to the effects of the complex Ι inhibitor rotenone. Western blot results also demonstrated that the constituent proteins of mitochondrial complex Ι were reduced by butyrate. Furthermore, mitochondria-dependent apoptosis has been shown to be initiated by inhibition of the complex Ι. Conclusion Collectively, our results revealed that butyrate inhibited the proliferation, migration and invasion of CC cells, and induced mitochondrial-dependent apoptosis by inhibiting mitochondrial complex Ι.
研究领域:
肿瘤学
·
细胞生物学
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分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2022
·
IF 12.545
Xia Liu,Lei Qin,Jie Yu,Wentao Sun,Jianhong Xu,Chun Li
During industrial fermentation , microbial cell factories are usually confronted with environmental or metabolic stresses, leading to the imbalance of intracellular redox and the reduction of cell metabolic capacity. Here, we constructed the genetically encoded redox biosensor system (RBS) based on redox-sensitive fluorescent proteins to detect redox metabolites , including reactive oxygen species (ROS), oxidized glutathione , NADH, and NADPH in Saccharomyces cerevisiae . The functional biosensors were quantitatively characterized and the orthogonal redox biosensor system (oRBS) was designed for detecting multiple redox metabolites. Furthermore, the compartment targeted redox biosensor system (ctRBS) was constructed to detect ROS and NADPH, revealing the distribution and spatiotemporal dynamics of ROS in yeast under various stress conditions. As a proof-of-concept, RBS was applied to evaluate the redox states of engineered yeast with stress resistance and heterogenous triterpene synthesis in vivo , elucidating the redox balance significantly affecting the growth and production phenotypes. The RBS in this study allowed the exploration of the diversity of compartmental redox state and real-time monitoring of the production process of yeast, providing a reliable and effective approach for accurate and in-depth profiling of bottlenecks of yeast cell factories.
研究领域:
生物技术
·
微生物学
·
分子生物学
·
系统生物学
✓ 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）