Biomed Research International
·
2018
·
IF 2.583
Xuemei Ye,Aifang Huang,Xianqin Wang,Congcong Wen,Lufeng Hu,Guanyang Lin
Linezolid has been widely used in serious infections for its effective inhibiting effect against multidrug-resistant gram-positive pathogens. However, linezolid caused severe adverse reactions, such as thrombocytopenia, anaemia, optic neuropathy, and near-fatal serotonin syndrome. In order to investigate the toxicity of linezolid, twenty-four Sprague-Dawley rats were randomly divided into: control group (n=7), low-group (n=8), and high-group (n=9). The rats of low-group and high-group were given by gavage with linezolid 60 and 120 mg/kg/day for 7 days, respectively. The serum concentration of linezolid was determined by high performance liquid chromatography (HPLC); blood metabolic change was analyzed by gas chromatography-mass spectrometer (GC-MS). Adenosine triphosphate (ATP) concentration in HepG2-C3A after being cultured with linezolid was determined by HPLC. The results showed that there were six metabolites and nine metabolites had statistical differences in low-group and high-group (P<0.05). The trimethyl phosphate was the most significant indicator in those changed metabolites. Except for d-glucose which was slightly increased in low-group, octadecanoic acid, cholest-5-ene, hexadecanoic acid, α-linolenic acid, eicosapentaenoic acid, 9,12-Octadecadienoic acid, and docosahexaenoic acid were all decreased in low-group and high-group. ATP concentration was decreased in HepG2-C3A after cultured with linezolid. In conclusion, the toxicity of linezolid is related to its serum concentration. Linezolid may inhibit the synthesis of ATP and fatty acid.
研究领域:
药理学
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毒理学
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代谢研究
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DOI
PubMed
高影响因子
Materials
·
2025
·Vol. 18
·期 6
·1351
·
IF 3.2
Ming Liu,Zhicun Liu,Xiangkai Qiao,Cheng Chen,Hongtu Guo,Hao Gu,Junbo Li,Tiedong Sun
Nanomotors driven by endogenous enzymes are favored in biology and pharmacy due to their spontaneous driving and efficient biocatalytic activity, and have potential applications in the treatment of clinical diseases that are highly dependent on targeted effects. For diseases such as muscle atrophy, using energy molecules such as ATP to improve cellular metabolism is a relatively efficient treatment method. However, traditional adenosine triphosphate (ATP) therapies for muscle atrophy face limitations due to instability under physiological conditions and poor targeting efficiency. To address these challenges, we developed an endogenous proton-gradient-driven ATP transport motor (ATM), a nanomotor integrating chloroplast-derived FoF1-ATPase with a biocompatible flask-shaped organic shell (FOS). The ATM is synthesized by vacuum-injecting phospholipid-embedded FoF1-ATPase nanothylakoids into ribose-based FOS, enabling autonomous propulsion in acidic microenvironments through proton-driven negative chemotaxis (directional movement away from regions of higher proton concentration). This nanomotor converts proton gradients into ATP synthesis, directly replenishing cellular energy deficits in atrophic tissues. In vitro studies demonstrated high biocompatibility (>90% cell viability at 150 μg/mL) and pH-responsive motility, achieving speeds up to 4.32 μm/s under physiological gradients (ΔpH = 3). In vivo experiments using dexamethasone-induced muscle atrophy mice revealed that ATM treatment accelerated weight recovery and restored normal muscle morphology, with treated mice exhibiting cell sizes comparable to healthy controls (30–40 μm vs. 15–25 μm in untreated). These results highlight the ATM’s potential as a precision therapeutic platform for metabolic disorders, leveraging the natural enzyme functionality and synthetic material design to enhance efficacy while minimizing systemic toxicity.
研究领域:
生物医学工程
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药理学
·
纳米医学
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DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Chao Gao,Ye Feng,Suyi Liu,Bin Chen,Miaomiao Ding,Dailing Du,Wenjing Zhang,Daniela A. Wilson,Yingfeng Tu,Fei Peng
Combining artificial cellular compartmentalization and intelligent motion benefits of micro/nanomotors, light is used as energy input to construct an artificial cell-based micromotor capable of photosynthetic anabolism and intelligent directional movement. This system is assembled from phospholipids functionalized with F-ATP synthase and molybdenum disulfide (MoS 2 ) nanoparticles (Vesical@MoS 2 -ATPase). The underlying mechanism involves the generation of protons (H + ) through photo-hydrolysis of MoS 2 nanoparticles within vesicles, which generates a local electroosmotic flow inside the vesicles and drives the negatively charged MoS 2 toward light. The established proton gradient across the phospholipid membrane, in turn, drives the ATP synthase to catalyze ATP production. Both in vitro and in vivo models demonstrate that the micromotor can elevate local intracellular ATP levels upon light and improve the metabolism of denatured chondrocytes. This cell mimicry, with capabilities of migration and biosynthesis, emerges as a promising platform for the next generation of functional bio-interface.
研究领域:
生物医学工程
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纳米医学
·
再生医学
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DOI
PubMed
高影响因子
AQUACULTURE
·
2023
·
IF 4.5
Xiang Liu,Bing-Ke Li,Qin-Xue Liu,Peng-Fei Li,Fei Ling,Gao-Xue Wang
Viral nervous necrosis (VNN) caused by nervous necrosis virus (NNV) is a major threat to the global aquaculture industry, resulting in huge economic losses. In this study, we evaluated a naturally anthraquinone, rhein, as a potential therapeutic agent against NNV. Rhein effectively inhibited NNV-induced cytopathic effects (CPE) at a concentration of 18.84 μM, with an inhibitory concentration (IC 50 ) against NNV replication of 8.77 μM. Moreover, the study revealed a possible anti-NNV mechanism. Rhein could disrupt NNV-induced S-phase cell cycle arrest by inhibiting ATP synthesis, and cell cycle arrested in S phase is favorable for NNV replication, which in turn inhibits NNV replication. The therapeutic effect of rhein was also evaluated in vivo , where the survival rate of NNV infected grouper was increased by 26.7% with the treatment of 10 mg/kg rhein. Our findings demonstrated the potential of rhein as a pharmacological compound that exerts significant antiviral activity against NNV by modulating the cell cycle and ATP synthesis. Consequently, rhein has shown significant promise as a medication for the prevention and treatment of viral infections in aquaculture.
研究领域:
水产养殖
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病毒学
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药理学
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DOI
高影响因子
mSphere
·
2025
·
IF 3.1
Xinda Li,Xiaoyi Luo,Bin Wang,Lei Fu,Xi Chen,Yu Lu
Drug-resistant tuberculosis (DR-TB) urgently requires safer, more accessible alternatives to bedaquiline (BDQ), which faces critical flaws like cardiotoxicity, high costs, and emerging resistance. WX-081, a promising BDQ alternative, has demonstrated superior anti-TB activity and improved safety in clinical studies. However, its mechanism of action remains unexplored, underscoring the need for further research to optimize its potential in advancing global TB elimination efforts. This study reveals WX-081’s dual mechanisms: targeting atpE to disrupt ATP synthase and proton motive force via resistance screening, gene sequencing, and functional assays while enhancing host immunity through macrophage transcriptomics. Molecular docking confirmed atpE binding sites, and immune activation pathways (NF-κB/MAPK) were identified, positioning WX-081 as a potent, safe anti-DR-TB candidate despite unresolved mechanistic details.
研究领域:
微生物学
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药物研发
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免疫学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2023
·
IF 6.1
Ying Gao,Jie Zhang,Jiexia Pan,Sanjun Ying,Bang Lou,Qingliang Yang,Weiyong Hong,Gensheng Yang
Aims To establish a F O F1-ATP synthase molecular motor biosensor to accurately identify colon cancer miRNAs. Main methods The F O F1-ATP synthase molecular motor is extracted by fragmentation–centrifugation and connected to the colon cancer-specific miR-17 capture probe in the manner of the ε subunit-biotin-streptavidin-biotin system. Signal probes are designed for dual-signal characterization to increase detection accuracy. The F O F1-ATPase rotation rate decreases when the signaling and capture probes are combined with the target miRNA, resulting in a decrease in ATP synthesis. miR-17 concentrations are determined by changes in ATP-mediated chemiluminescence intensity and signal probe-mediated OD 450nm . Key findings The chemiluminescence intensity and OD 450nm show a good linear relationship with the miR-17 concentration in the range of 5 to 200 nmol L −1 (R 2 = 0.9985, 0.9989). The colon cancer mouse model is established for the blood samples, and miR-17 in serum and RNA extracts is quantitatively determined using the constructed sensor. Significance The results are consistent with colon cancer progression, and the low concentration of miR-17 detecting accuracy is comparable to the PCR assay. In conclusion, the developed method is a direct, rapid, and promising method for miRNA detection of colon cancer.
研究领域:
生物化学
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分子生物学
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癌症研究
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生物技术
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Yu Ma,Wei Yang,Peiyao Liang,Ruzhen Feng,Tianming Qiu,Jingyuan Zhang,Xiance Sun,Qiujuan Li,Guang Yang,Xiaofeng Yao
As a persistent organic pollutant, perfluorooctane sulfonate (PFOS) has a serious detrimental impact on human health. It has been suggested that PFOS is associated with liver inflammation. However, the underlying mechanisms are still unclear. Here, PFOS was found to elevate the oligomerization tendency of voltage-dependent anion channel 1 (VDAC1) in the mice liver and human normal liver cells L-02. Inhibition of VDAC1 oligomerization alleviated PFOS-induced nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome activation. Cytoplasmic membrane VDAC1 translocated to mitochondria was also observed in response to PFOS. Therefore, the oligomerization of VDAC1 occurred mainly in the mitochondria. VDAC1 was found to interact with the ATP synthase beta subunit (ATP5B) under PFOS treatment. Knockdown of ATP5B or immobilization of ATP5B to the cytoplasmic membrane alleviated the increased VDAC1 oligomerization and NLRP3 inflammasome activation. Therefore, our results suggested that PFOS induced NLRP3 inflammasome activation through VDAC1 oligomerization, a process dependent on ATP5B to transfer VDAC1 from the plasma membrane to the mitochondria. The findings offer novel perspectives on the activation of the NLRP3 inflammasome, the regulatory mode on VDAC1 oligomerization, and the mechanism of PFOS toxicity.
研究领域:
毒理学
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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
JOURNAL OF PROTEOME RESEARCH
·
2016
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IF 4.173
Zhilei Liu,Yadong Hu,Haisha Liang,Zhongyuan Sun,Shan Feng,Haiteng Deng
PRDX3 is a mitochondrial peroxide reductase that regulates cellular redox state. It has been reported that PRDX3 is overexpressed in liver cancer, but how PRDX3 is involved in hepatocellular carcinoma (HCC) tumorigenesis and progression has not been well-characterized. In the present study, we established two stable cell lines by overexpressing or knocking down PRDX3 in HepG2 cells. We found that PRDX3 silencing decreased the growth rate of HepG2 cells and increased mtDNA oxidation. Quantitative proteomics identified 475 differentially expressed proteins between the PRDX3 knockdown and the control cells. These proteins were involved in antioxidant activity, angiogenesis, cell adhesion, cell growth, ATP synthesis, nucleic acid binding, redox, and chaperones. PRDX3 knockdown led to the down-regulation of ATP synthases and the decreased cellular ATP level, contributing to the slow-down of cell growth. Furthermore, silencing PRDX3 enhanced invasive properties of HepG2 cells via TIMP-1 down-regulation and the increased ECM degradation. Taken together, our results indicate that PRDX3 promotes HCC growth and mediates cell migration and invasiveness and is a potential therapeutic target for HCC treatment.
研究领域:
肿瘤学
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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
Scientific Reports
·
2017
·
IF 4.259
Xie Xiaoyun,Han Chaofei,Zeng Weiqi,Chen Chen,Lu Lixia,Liu Queping,Peng Cong,Zhao Shuang,Su Juan,Chen Xiang
The F1F0-ATP synthase, an enzyme complex, is mainly located on the mitochondrial inner membrane or sometimes cytomembrane to generate or hydrolyze ATP, play a role in cell proliferation. This study focused on the role of F1F0-ATP synthase in keratinocyte differentiation, and its relationship with intracellular and extracellular ATP (InATP and ExATP). The F1F0-ATP synthase β subunit (ATP5B) expression in various skin tissues and confluence-dependent HaCaT differentiation models was detected. ATP5B expression increased with keratinocyte and HaCaT cell differentiation in normal skin, some epidermis hyper-proliferative diseases, squamous cell carcinoma, and the HaCaT cell differentiation model. The impact of InATP and ExATP content on HaCaT differentiation was reflected by the expression of the differentiation marker involucrin. Inhibition of F1F0-ATP synthase blocked HaCaT cell differentiation, which was associated with a decrease of InATP content, but not with changes of ExATP. Our results revealed that F1F0-ATP synthase expression is associated with the process of keratinocyte differentiation which may possibly be related to InATP synthesis.
研究领域:
细胞生物学
·
分子生物学
·
皮肤病学
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产品关联
DOI
PubMed
高影响因子
Probiotics and Antimicrobial Proteins
·
2022
·Vol. 15
·期 2
·400-410
·
IF 5.265
Huang Yu-Ping,Shi Jie-Yan,Luo Si-Chen,Xu Shao-Yan,Zhang Jia-Dong,Molnár István,Yang Qiong-Qiong,Zhang Bo-Bo
Bacterial vaginosis (BV) is a common vaginal disease associated with abnormal changes in the vaginal microbiome. Our previous study found that Lactobacillus rhamnosus has a good therapeutic effect on bacterial vaginosis by inhibiting the most prominent bacterium associated with BV, Gardnerella vaginalis . In this study, we show that acetic acid and lactic acid are the main substances in the cell-free supernatant (CFS) of L. rhamnosus that inhibit the growth of G. vaginalis. Further study on the mechanism showed that acetic acid and lactic acid alter the morphology of the G. vaginalis cells, eventually causing the cells to shrink or burst, resulting in exudation of their intracellular contents. In addition, these two organic acids also dissipate the membrane potential of bacterial cells, affecting their synthesis of ATP. A reduced activity of the Na + /K + -ATPase leads to abnormal ATP metabolism, and ultimately inhibits the growth and reproduction of G. vaginalis . Our study provides valuable information for the widespread application of L. rhamnosus in the treatment of bacterial vaginosis.
研究领域:
微生物学
·
传染病
·
女性健康
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DOI
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
·
分子生物学
·
药理学
·
传染病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL BOTANY
·
2023
·
IF 6.9
He Chengyong,Xing Fei,Liang Jiahui,Zhang Zhixiang,Zhan Binhui,Habili Nuredin,Wang Hongqing,Li Shifang
Apple necrotic mosaic virus (ApNMV) is associated with apple mosaic disease in China. However, the mechanisms of ApNMV infection, as well as host defence against the virus, are still poorly understood. Mitochondrial ATP synthase plays a fundamental role in the regulation of plant growth and development. However, mitochondrial ATP synthase function in response to virus infection remains to be defined. In the present study, a yeast two-hybrid (Y2H) screening revealed that the apple mitochondrial ATP synthase oligomycin sensitivity-conferring protein (OSCP) subunit (MdATPO) interacts with ApNMV coat protein (CP). It was further verified that overexpression of MdATPO in Nicotiana benthamiana inhibited viral accumulation. In contrast, silencing of NbATPO facilitated viral accumulation, indicating that ATPO plays a defensive role during ApNMV infection. Further investigation demonstrated that ApNMV infection accelerated abscisic acid (ABA) accumulation, and ABA negatively regulated ATPO transcription, which was related to the ability of ABA insensitive 5 (ABI5) to bind to the ABA-responsive elements (ABREs) of the ATPO promoter. Taken together, our results indicated that transcription factor ABI5 negatively regulated ATPO transcription by directly binding to its promoter, leading to the susceptibility of apple and N. benthamiana to ApNMV infection. The current study facilitates a comprehensive understanding of the intricate responses of the host to ApNMV infection.
研究领域:
植物病理学
·
分子生物学
·
病毒学
·
植物生理学
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产品关联
DOI
PubMed
高影响因子
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