CANCER LETTERS
·
2017
·
IF 6.375
Changzheng Wang,Hongwei Lv,Wen Yang,Ting Li,Tian Fang,Guishuai Lv,Qin Han,Liwei Dong,Tianyi Jiang,Beige Jiang,Guangshun Yang,Hongyang Wang
Cholangiocarcinoma (CC) is a devastating malignancy with late diagnosis and poor response to conventional chemotherapy. Recent studies have revealed anti-cancer effect of vitamin C ( l -ascorbic acid, ascorbate) in several types of cancer. However, the effect of l -ascorbic acid (AA) in CC remains elusive. Herein, we demonstrated that AA induced cytotoxicity in CC cells by generating intracellular reactive oxygen species (ROS), and subsequently DNA damage, ATP depletion, mTOR pathway inhibition. Moreover, AA worked synergistically with chemotherapeutic agent cisplatin to impair CC cells growth both in vitro and in vivo. Intriguingly, sodium-dependent vitamin C transporter 2 (SVCT-2) expression was inversely correlated with IC50 values of AA. Knockdown of SVCT-2 dramatically alleviated DNA damage, ATP depletion, and inhibition of mTOR pathway induced by AA. Furthermore, SVCT-2 knockdown endowed CC cells with the resistance to AA treatment. Finally, the inhibitory effects of AA were further confirmed in patient-derived CC xenograft models. Thus, our results unravel therapeutic potential of AA alone or in combination with cisplatin for CC. SVCT2 expression level may serve as a positive outcome predictor for AA treatment in CC.
研究领域:
肿瘤学
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药理学
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分子生物学
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PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Ting-ting Huang,Yan-ni Liu,Jin-Xian Huang,Ping-ping Yan,Jijing Wang,Yong-xiao Cao,Lei Cao
Due to the emergence and spread of multidrug resistance in Helicobacter pylori ( H. pylori ), its eradication has become difficult. Sodium sulfite (SS), a widely used food additive for ensuring food safety and storage, has been recognized as an effective nonbactericidal agent for H. pylori eradication. However, the mechanism by which H. pylori adapts and eventually succumbs under low- or no-oxygen conditions remains unknown. In this study, we aimed to evaluate the anti- H. pylori effect of SS and investigated the multiomics mechanism by which SS kills H. pylori . The results demonstrated that SS effectively eradicated H. pylori both in vitro and in vivo . H. pylori responds to the oxygen changes regulated by SS, downregulates the HcpE gene, which is responsible for redox homeostasis in bacteria, decreases the activities of enzymes related to oxidative stress, and disrupts the outer membrane structure, increasing susceptibility to oxidative stress. Furthermore, SS downregulates the content of cytochrome C in the microaerobic respiratory chain, leading to a sharp decrease in ATP synthesis. Consequently, the accumulation of triglycerides (TGs) in bacteria due to oxidative stress supports anaerobic respiration, meeting their energy requirements. The multifaceted death of H. pylori caused by SS does not result in drug resistance. Thus, screening of the redox homeostasis of HcpE as a new target for H. pylori infection treatment could lead to the development of a novel approach for H. pylori eradication therapy.
研究领域:
微生物学
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分子生物学
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药理学
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传染病学
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PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
·
IF 12.2
Kunlong Yang,Yue Luo,Tongzheng Sun,Han Qiu,Qingru Geng,Yongxin Li,Man Liu,Nancy P. Keller,Fengqin Song,Jun Tian
Nitric oxide (NO) is a signaling molecule with diverse roles in various organisms. However, its role in the opportunistic pathogen Aspergillus flavus remains unclear. This study investigates the potential of NO, mediated by metabolites from A. oryzae (AO), as an antifungal strategy against A . flavus . We demonstrated that AO metabolites effectively suppressed A . flavus asexual development, a critical stage in its lifecycle. Transcriptomic analysis revealed that AO metabolites induced NO synthesis genes, leading to increased intracellular NO levels. Reducing intracellular NO content rescued A . flavus spores from germination inhibition caused by AO metabolites. Furthermore, exogenous NO treatment and dysfunction of flavohemoglobin Fhb1, a key NO detoxification enzyme, significantly impaired A . flavus asexual development. RNA-sequencing and metabolomic analyses revealed significant metabolic disruptions within tricarboxylic acid (TCA) cycle upon AO treatment. NO treatment significantly reduced mitochondrial membrane potential (Δψm) and ATP generation. Additionally, aberrant metabolic flux within the TCA cycle was observed upon NO treatment. Further analysis revealed that NO induced S-nitrosylation of five key TCA cycle enzymes. Genetic analysis demonstrated that the S-nitrosylated Aconitase Acon and one subunit of succinate dehydrogenase Sdh2 played crucial roles in A . flavus development by regulating ATP production. This study highlights the potential of NO as a novel antifungal strategy to control A . flavus by compromising its mitochondrial function and energy metabolism.
研究领域:
微生物学
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分子生物学
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真菌学
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生物化学
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DOI
PubMed
高影响因子
Food Bioscience
·
2018
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IF 2.371
Guan Wang,Manman Liu,Liwei Cao,Jirawat Yongsawatdigul,Shanbai Xiong,Ru Liu
The effect of NaCl (0.1 − 3.0 M) on self-assembly of silver carp myosin at 4 °C was investigated in terms of microstructure, conformation, intermolecular interactions, and particle size distribution. During setting at 4 °C, the self-assembly of myosin showed an obvious concentration dependence. At low concentrations (<0.3 M), myosin assembled into filaments mainly through rod-rod ionic linkages, and showed significantly (P < 0.05) higher turbidity and lower solubility than at ≥0.3 M. The addition of NaCl (0.3 − 0.6 M) led to the extension and dissolution of myosin by interfering with electrostatic interactions. The myosin assemblies gradually became smaller and more uniform. The solubility and Ca 2+ -ATPase activity reached a maximum at 0.6 M NaCl. When the concentrations increased to >1.0 M, myosin further assembled into filaments dominated by hydrophobic interactions. Both rod-rod and head-head interactions contributed to the myosin filaments at high concentrations (1.0 − 3.0 M). The solubility and uniformity of the myosin assemblies decreased as the NaCl concentration increased from 1.0 to 3.0 M.
研究领域:
食品科学
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蛋白质化学
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生物物理学
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DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2024
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IF 8
Yani Liu,Haoyu Chen,Lin Chai,Jing Liu,Shu Huang,Feng Liu,Mingjie Wei,Xiaohua Zhu,Youyu Zhang,Meiling Liu,Shouzhuo Yao
The simultaneous or continuous detection of multiple targets in complex samples is for various applications, notably in medical diagnostics and environmental monitoring. A novel dual-channel colorimetric and fluorescent method has been developed for the continuous detection of adenosine triphosphate (ATP) and copper ions based on PCN-224@Fe 2 O 3 , which exhibits both fluorescent and enhanced peroxidase-like (POD-like) properties. The synthesis of PCN-224@Fe 2 O 3 involved the in-situ growth of ferric oxide on Zr-based metal-organic frameworks (PCN-224). Through catalyzing the colorless compound 3,3′,5,5′-tetramethylbenzidine (TMB) to produce a blue product (oxTMB) in the presence of H 2 O 2 , PCN-224@Fe 2 O 3 allows for the detection of ATP and copper ions . The unique mechanism involves ATP weakening the POD-like activity of PCN-224@Fe 2 O 3 by forming Zr-O-P bonds with Zr in PCN-224, which also leads to fluorescence recovery. Copper ions, through chelating with ATP, counteract the effect of ATP on PCN-224@Fe 2 O 3 , resulting in increased POD-like activity and the amount of oxTMB alongside the quenching of the fluorescence of the system. This facilitates colorimetric “on-off-on” and fluorescence “off-on-off” switch sensing for ATP and Cu 2+ . The application of PCN-224@Fe 2 O 3 in the detection of ATP and Cu 2+ in human serum yielded satisfactory results. This innovative approach not only provides a means to regulate the mimic activity of oxides but also presents a convenient, sensitive, and accurate detection method for ATP and Cu 2+ , significantly broadening the potential application of MOFs and nanozymes in bioanalysis .
研究领域:
生物分析
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环境监测
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医学诊断
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高影响因子
JOURNAL OF SOLID STATE ELECTROCHEMISTRY
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2021
·Vol. 25
·期 3
·1073-1081
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IF 2.647
Jin Xin,Lv Mengmeng,Pan Qing,Fang Shu,Zhu Ningning
We describe a label-free electrochemical aptasensor for adenosine triphosphate (ATP) assay based on bifunctional Fe 3 O 4 @Au nanocomposites. Due to the introduction of Au nanoparticles, the resulting bifunctional Fe 3 O 4 @Au nanocomposites can be easily modified with ATP-specific aptamer molecules through Au–S interaction to build the nanoprobe and used to immobilize on a glassy carbon electrode simply with the assistance of a magnet. Once exposed to the target ATP, the current signal obtained at nanoprobe-containing magnetic glassy carbon electrode decreases immediately. The decrease in sensor current is a result of the less methylene blue adsorbed on the aptamer caused by the fact that the ATP-specific aptamer prefers to bind with ATP rather than with methylene blue. The decrease in sensor current can be used for electrochemical determination of ATP, for example, to determine ATP in human serum samples.
研究领域:
分析化学
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生物传感器
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纳米技术
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电化学
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DOI
高影响因子
Nature Communications
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2024
·Vol. 15
·期 1
·1-12
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IF 14.7
Li Guangjian,Liang Hui,Gao Ruichen,Qin Ling,Xu Pei,Huang Mingtao,Zong Min-Hua,Cao Yufei,Lou Wen-Yong
Microbial biosynthesis has become the leading commercial approach for large-scale production of terpenoids, a valuable class of natural products. Enhancing terpenoid production, however, requires complex modifications on the host organism. Recently, a two-step isopentenol utilization (IU) pathway relying solely on ATP as the cofactor has been proposed as an alternative to the mevalonate (MVA) pathway, streamlining the synthesis of the common terpenoid precursors. Herein, we find that isopentenol inhibits energy metabolism, leading to reduced efficiency of the IU pathway in Saccharomyces cerevisiae . To overcome this, we engineer an IU pathway-dependent (IUPD) strain, designed for growth-coupled production. The IUPD strain is compelled to enhance the ATP supply, essential for the IU pathway, and incorporates a high-throughput screening method for enzyme evolution. The refined IU pathway surpasses the MVA pathway in synthesizing complex terpenoids. Our work offers valuable insights into developing growth-coupled strains adapted to efficient natural product synthesis.
研究领域:
微生物学
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代谢工程
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生物技术
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生物化学
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DOI
PubMed
高影响因子
IMMUNITY
·
2024
·
IF 25.5
Jingjing Cong,Pianpian Liu,Zili Han,Wei Ying,Chaoliang Li,Yifei Yang,Shuling Wang,Jianbo Yang,Fei Cao,Juntao Shen,Yu Zeng,Yu Bai,Congzhao Zhou,Lilin Ye,Rongbin Zhou,Chunjun Guo,Chunlei Cang,Dennis L. Kasper,Xinyang Song,Lei Dai,Linfeng Sun,Wen Pan,Shu Zhu
Concentrations of the secondary bile acid, deoxycholic acid (DCA), are aberrantly elevated in colorectal cancer (CRC) patients, but the consequences remain poorly understood. Here, we screened a library of gut microbiota-derived metabolites and identified DCA as a negative regulator for CD8 + T cell effector function. Mechanistically, DCA suppressed CD8 + T cell responses by targeting plasma membrane Ca 2+ ATPase (PMCA) to inhibit Ca 2+ -nuclear factor of activated T cells (NFAT)2 signaling. In CRC patients, CD8 + T cell effector function negatively correlated with both DCA concentration and expression of a bacterial DCA biosynthetic gene. Bacteria harboring DCA biosynthetic genes suppressed CD8 + T cells effector function and promoted tumor growth in mice. This effect was abolished by disrupting bile acid metabolism via bile acid chelation, genetic ablation of bacterial DCA biosynthetic pathway, or specific bacteriophage. Our study demonstrated causation between microbial DCA metabolism and anti-tumor CD8 + T cell response in CRC, suggesting potential directions for anti-tumor therapy.
研究领域:
肿瘤学
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免疫学
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微生物学
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PubMed
高影响因子
PLANT PHYSIOLOGY AND BIOCHEMISTRY
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2024
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IF 6.1
Chenghao Huang,Fei Huang,Xuke Wang,Dongru Wang,Jiawei Wang,Xinhua Zhan
Polycyclic aromatic hydrocarbons (PAHs) constitute a category of persistent organic contaminants that possess the potential to induce carcinogenic, teratogenic, and mutagenic consequences. Our previous findings have revealed that plant roots actively take up PAHs through co-transport with protons, and auxin can promote PAHs uptake by wheat roots. It remains unclear whether nitric oxide (NO), a signaling molecule involved in numerous physiological processes in plants and downstream of auxin, can affect PAHs uptake by plant roots. In our study, 50 μmol/L sodium nitroprusside (SNP) significantly enhanced phenanthrene uptake after 4 h of exposure. After the addition of SNP (50 μmol/L), the H + flux on root surface increased, and H + -ATPase activity was activated, indicating that exogenous NO promotes phenanthrene uptake by plant roots via activating H + -ATPase. By studying the effects of 50 μmol/L cyclic guanosine monophosphate (cGMP), 5 mmol/L Ca 2+ , and 50 μmol/L adenosine monophosphate (AMP) on phenanthrene uptake by ryegrass roots and measuring root calcium-dependent protein kinases (CDPK) activity, we demonstrated that exogenous NO promotes phenanthrene uptake through the signaling pathway of NO, cGMP, Ca 2+ , CDPK, 14-3-3 protein and H + -ATPase. The results contribute significant insights into elucidating the underlying mechanisms of NO modulating PAHs absorption by plant roots, thereby offering crucial strategies for advancing food safety measures and enhancing the phytoremediation potential of soils and waters contaminated with PAHs.
研究领域:
环境科学
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植物生理学
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植物修复
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土壤污染
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DOI
PubMed
高影响因子
JOURNAL OF FOOD PROTECTION
·
2018
·
IF 1.51
Jinrong Bai,Yanping Wu,Kai Zhong,Kai Xiao,Lijin Liu,Yina Huang,Zhengshu Wang,Hong Gao
ABSTRACT Quinic acid (QA) and shikimic acid (SA), two kinds of natural organic acids, have been reported to exhibit potent antibacterial activity against Staphylococcus aureus . In this study, the effects of QA and SA on the cellular functions of S. aureus were investigated by measuring the intracellular pH, intracellular and extracellular ATP concentrations, succinate dehydrogenase activity, DNA content, and interactions between SA and QA with S. aureus DNA. Studies of the cellular functions demonstrated that QA could significantly decrease the intracellular pH, whereas SA had no effect on intracellular pH. QA and SA reduced succinate dehydrogenase activity and caused a significant decrease in intracellular ATP concentration but no proportional increase in extracellular ATP. Moreover, QA and SA both could remarkably reduce the DNA content of S. aureus and directly interact with genomic DNA. The results suggested that the effects of QA and SA on cellular functions were distinguishable, although the chemical structures of these two compounds were similar. In conclusion, the results of the present research suggested that SA and QA could be used as antibacterial agents in food preservation.
研究领域:
微生物学
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生物化学
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食品科学
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PubMed
高影响因子
MICROCHIMICA ACTA
·
2021
·Vol. 188
·期 2
·1-9
·
IF 5.833
Li Wenjun,Chen Siyu,Yang Yue,Song Yiju,Ma Chaoyun,Qiao Xiuwen,Hong Chenglin
A GOx/HRP@ZIF-90 nanomaterial is proposed by coating GOx and HRP in ZIF-90 using a bio-simulated mineralization method to improve the tolerance of the enzyme to the external environment. In the detection process, the ZIF-90 is turned on under mild conditions by the competitive reaction of ATP with Zn 2+ and imidazole-2-carboxaldehyde (2-ICA), and the electrical signal of the system is amplified by the enzyme cascade reaction of GOx and HRP. Finally, based on the signal amplification strategy of the competitive reaction between Zn 2+ and ATP to construct a “signal on” mode, electrochemical immunosensor of GOx-HRP enzyme–linked cascade reaction was prepared. The proposed electrochemical immunosensor shows an excellent analytical performance when detecting CA-125, with good selectivity and stability, with a detection range of 0.1 pg mL −1 –40 ng mL −1 and a detection limit of 0.05 pg mL −1 . The test has been performed using chronoamperometry under a constant voltage of −0.4 V. The immunosensor also shows an excellent performance when analysing human blood samples. The recovery of the immunosensor is 97.94–101.8%, with a relative standard deviation of 3.7–6.1%. The proposed sensor provides a novel idea for clinical use of GOx and HRP enzymes and a new method for the clinical detection of tumor markers. Graphical abstract
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JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Ziwei Guo,Huan He,Kunqian Liu,Zihui Li,Yanting Xi,Zhicheng Liao,Guohua Dao,Bin Huang,Xuejun Pan
Increasing antivirals in surface water caused by their excessive consumption pose serious threats to aquatic organisms . Our recent research found that the input of antiviral drug arbidol to algal bloom water can induce acute toxicity to the growth and metabolism of Microcystis aeruginosa , resulting in growth inhibition, as well as decrease in chlorophyll and ATP contents. However, the toxic mechanisms involved remained obscure, which were further investigated through transcriptomic analysis in this study. The results indicated that 885–1248 genes in algae were differentially expressed after exposure to 0.01–10.0 mg/L of arbidol, with the majority being down-regulated. Analysis of commonly down-regulated genes found that the cellular response to oxidative stress and damaged DNA bonding were affected, implying that the stress defense system and DNA repair function of algae might be damaged. The down-regulation of genes in porphyrin metabolism, photosynthesis , carbon fixation , glycolysis, tricarboxylic acid cycle , and oxidative phosphorylation might inhibit chlorophyll synthesis, photosynthesis, and ATP supply, thereby hindering the growth and metabolism of algae. Moreover, the down-regulation of genes related to nucleotide metabolism and DNA replication might influence the reproduction of algae. These findings provided effective strategies to elucidate toxic mechanisms of contaminants on algae in algal bloom water.
研究领域:
环境科学
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毒理学
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分子生物学
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水生生态学
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PubMed
高影响因子
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