SENSORS AND ACTUATORS B-CHEMICAL
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2022
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IF 9.221
Xuegang Li,Pengqi Gong,Qiming Zhao,Xue Zhou,Yanan Zhang,Yong Zhao
A novel DNA hybridization optical fiber sensor with temperature and pH compensation for detecting a common lung cancer gene of epidermal growth factor receptor (EGFR) gene was demonstrated in this paper. The paper proposes the first research to achieve dual surface plasmon resonance (SPR) in an Fiber Bragg grating (FBG) and implement a three-parameter detection of DNA sequence , temperature and pH using a single fiber. Probe DNA sequences (pDNA) and PAA/CS, a pH-sensitive material, are immobilized on the sensor surface for EGFR gene exon-20 detection and temperature and pH monitoring simultaneously. The effectiveness of this functionalized method has been proved by using an atomic force microscope (AFM) and scanning electron microscope (SEM). The limit of detection (LOD) of EGFR gene was experimentally verified to 13.5 nM. The advantages of fast response, high sensitivity, label free, plug in, low LOD and three-parameter detection demonstrated by this sensor in the experiment are important for the field of DNA hybridization research and solving the problems of biosensor susceptibility to temperature and pH.
研究领域:
生物医学工程
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分子生物学
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光学传感
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DOI
高影响因子
Journal of Extracellular Vesicles
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2023
·Vol. 12
·期 9
·12364
·
IF 16
Jie He,Hengyu Li,John Mai,Yuqing Ke,Chunhui Zhai,Jiao Jiao Li,Lai Jiang,Guangxia Shen,Xianting Ding
Extracellular vesicle (EV) surface proteins, expressed by primary tumours, are important biomarkers for early cancer diagnosis. However, the detection of these EV proteins is complicated by their low abundance and interference from non-EV components in clinical samples. Herein, we present a MEmbrane-Specific Separation and two-step Cascade AmpLificatioN (MESS2CAN) strategy for direct detection of EV surface proteins within 4 h. MESS2CAN utilises novel lipid probes (long chains linked by PEG2K with biotin at one end, and DSPE at the other end) and streptavidin-coated magnetic beads, permitting a 49.6% EV recovery rate within 1 h. A dual amplification strategy with a primer exchange reaction (PER) cascaded by the Cas12a system then allows sensitive detection of the target protein at 10 EV particles per microliter. Using 4 cell lines and 90 clinical test samples, we demonstrate MESS2CAN for analysing HER2, EpCAM and EGFR expression on EVs derived from cells and patient plasma. MESS2CAN reports the desired specificity and sensitivity of EGFR (AUC = 0.98) and of HER2 (AUC = 1) for discriminating between HER2-positive breast cancer, triple-negative breast cancer and healthy donors. MESS2CAN is a pioneering method for highly sensitive in vitro EV diagnostics, applicable to clinical samples with trace amounts of EVs.
研究领域:
生物技术
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医学诊断
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癌症研究
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分子生物学
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DOI
PubMed
高影响因子
iScience
·
2021
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IF 5.458
Xidong Yang,Meiyan Liao,Hanfei Zhang,JinBo Gong,Fan Yang,Mengying Xu,Pier-Luc Tremblay,Tian Zhang
Summary A liquid biopsy is a noninvasive approach for detecting double-stranded circulating tumor DNA (ctDNA) of 90–320 nucleotides in blood plasma from patients with cancer. Most techniques employed for ctDNA detection are time consuming and require expensive DNA purification kits. Electrochemiluminescence resonance energy transfer (ECL-RET) biosensors exhibit high sensitivity, a wide response range, and are promising for straightforward sensing applications. Until now, ECL-RET biosensors have been designed for sensing short single-stranded oligonucleotides of less than 45 nucleotides. In this work, an ECL-RET biosensor comprising graphitic carbon nitride quantum dots was assessed for the amplification-free detection in the blood plasma of DNA molecules coding for the EGFR L858R mutation, which is associated with non-small-cell lung cancer. Following a low-cost pre-treatment, the highly specific ECL-RET biosensor quantified double-stranded EGFR L858R DNA of 159 nucleotides diluted into the blood within a linear range of 0.01 fM to 1 pM, demonstrating its potential for noninvasive biopsies.
研究领域:
医学诊断
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生物传感技术
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癌症研究
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
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IF 6.7
Hongyan Lin,Hongwei Han,Minkai Yang,Zhongling Wen,Qingqing Chen,Yudi Ma,Xuan Wang,Changyi Wang,Tongming Yin,Xiaoming Wang,Guihua Lu,Hongyuan Chen,Jinliang Qi,Yonghua Yang
Pyruvate kinase 2 (PKM2) and pyruvate dehydrogenase kinase 1 (PDK1) are two key enzymes in tumor glucose metabolism pathway that not only promote tumor growth and proliferation through accelerating aerobic glycolysis , but also contribute to drug resistance of non-small cell lung cancer (NSCLC). Considering that targeting PKM2 or PDK1 alone seems insufficient to remodel abnormal glucose metabolism to achieve significant antitumor activity , we proposed a “two-step approach” that regulates PKM2 and PDK1 synchronously. Firstly, we found that the combination of ML265 (PKM2 activator) and AZD7545 (PDK1 inhibitor) could synergistically inhibit proliferation and induce apoptosis in H1299 cells. Base on this, we designed a series of novel shikonin ( SK ) thioether derivatives as PKM2/PDK1 dual-target agents, among which the most potent compound E5 featuring a 2-methyl substitution on the benzene ring exerted significantly increased inhibitory activity toward EGFR mutant NSCLC cell H1975 (IC 50 = 1.51 μmol/L), which was 3 and 17-fold more active than the lead compound SK (IC 50 = 4.56 μmol/L) and the positive control gefitinib (IC 50 = 25.56 μmol/L), respectively. Additionally, E5 also showed good anti-tumor activity in xenografted mouse models, with significantly lower toxicity side effects than SK . Moreover, E5 also inhibited the entry of PKM2 into nucleus to regulate the transcriptional activation of oncogenes , thus restoring the sensitivity of H1975 cell to gefitinib. Collectively, these data demonstrate that E5 , a dual inhibitor of PKM2/PDK1, may be a promising adjunct to gefitinib in the treatment of EGFR-TKIs resistant NSCLC, deserving further investigation.
研究领域:
肿瘤学
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药理学
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癌症生物学
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代谢途径
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DOI
PubMed
高影响因子
ONCOGENE
·
2024
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IF 6.9
Shi Jie,Zhou Rui,Wang Shuo,Liu Yuxin,Tian Baorui,Liu Yanhua,Chen Yanan,Hu Taoyu,Mu Yuhao,Wang Shufan,Shao Xintao,Yan Jie,Qu Pengpeng,Wei Ding,Yang Shuang,Shi Yi,Li Jia,Wang Longlong
Glycosylation profoundly influences the interactions between cancer cells and microenvironmental stromal cells during the peritoneal disseminated metastasis of ovarian carcinoma (OC), which is the major cause of cancer-related death. Although the characteristic cancer glycoconjugates are widely used as biomarkers for cancer diagnosis, our knowledge about cancer glycome remains quite fragmented due to the technique limitations in analyzing glycan chains with tremendous structural and functional heterogeneity. Given the dysregulated cancer glycome is defined by the altered glycosylation machinery, here we performed a systematic loss-of-function screen on 498 genes involved in glycosylation for key regulators of OC dissemination. We identified neuraminidase 4 (NEU4), an enzyme capable of hydrolyzing terminal sialic acid from glycoconjugates, as a vital peritoneal dissemination-promoting modifier of OC glycome. In human patients with high-grade serous OC (HGSOC), increased NEU4 was detected in the disseminated OC cells when compared with that in the primary tumor cells, which significantly correlated with the worse survival. Among three alternative splice-generated isoforms of human NEU4, we revealed that only the plasma membrane-localized NEU4 isoform 2 (NEU4-iso2) and intracellular isoform 3 promoted the peritoneal dissemination of OC by enhancing the cell motility and epithelial-mesenchymal transition. We also identified NEU4-iso2-regulated cell surface glycoproteome and found that NEU4-iso2 desialylated the epithelial growth factor receptor (EGFR), in particular at N 196 residue, for the hyperactivation of EGFR and its downstream tumor-promoting signaling cascades. Our results provide new insights into how the OC glycome is dysregulated during OC progression and reveal a functionally important glycosite on EGFR for its abnormal activation in cancer.
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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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Chinese Journal of Integrative Medicine
·
2022
·Vol. 29
·期 3
·244-252
·
IF 2.626
Wang Yuan-chun,Hui Jian-rong,Xiao Gang,Ma Qiao-lin
Objective To investigate the mechanism of the effect of Astragalus membranaceus ( A. membranaceus ) on lung adenocarcinoma at the molecular level to elucidate the specific targets according to the network pharmacology approach. Methods The active components of A. membranaceus and their potential targets were collected from the Traditional Chinese Medicine Systems Pharmacology Database. Lung adenocarcinoma-associated genes were acquired based on GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGKB, and Therapeutic Targets databases. The PI3K/AKT signaling pathway-related genes were obtained using Reactome portal. Networks of “ingredient-target” and “ingredient-target-pathway-disease” were constructed using the Cytoscape3.6.0 software. The relationships among targets were analyzed according protein-protein interaction (PPI) network. Finally, molecular docking was applied to construct the binding conformation between active ingredients and core targets. Cell counting kit 8 (CCK8) and Western blot assays were performed to determine the mechanism of the key ingredient of A. membranaceus . Results A total of 20 active components and their 329 targets, and 7,501 lung adenocarcinoma-related genes and 130 PI3K/AKT signaling pathway-related genes were obtained. According to Venn diagram and PPI network analysis, 2 mainly active ingredients, including kaempferol and quercetin, and 6 core targets, including TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR, were identified. The two important active ingredients of A. membranaceus , kaempferol and quercetin, exert the therapeutic effect in lung adenocarcinoma partly by acting on the 6 core targets (TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR) of PI3K/AKT signaling pathway. Expressions of potential targets in lung adenocarcinoma and normal samples were analyzed by using UALCAN portal and found that ERBB2 was overexpressed in lung adenocarcinoma tissues and upregulation of it correlated with clinicopathological characteristics. Finally, quercetin repressed viabilities of lung adenocarcinoma cells by targeting ERBB2 on PI3K/AKT signaling confirmed by CCK8 and Western blot. Conclusion Our finding unraveled that an active ingredient of A. membranaceus , quercetin, significantly inhibited the lung adenocarcinoma cells proliferation by repressing ERBB2 level and inactivating the PI3K/AKT signaling pathway.
研究领域:
药理学
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肿瘤学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Min Luo,Yuxin Lou,Yingqi Liang,Jiangang Mei,Di Zhang,Fei Lan,Junfang Zhu,Yuxin Fang,Lei Zheng,Shihua Luo,Ye Zhang
Extracellular vesicles (EVs) contain a wealth of biological information and hold great value for disease diagnosis. In contrast to conventional in vitro detection, in vivo detection has the ability to improve the detection efficiency, reduce external interferences and enable continuous or real-time dynamic monitoring. However, developing a simple and accurate in vivo assay for EVs remains challenging. In this study, we constructed an allosteric aptamer-based flexible microneedle biosensor capable of measuring disease-associated EVs in vivo. Firstly, the aptamer binding to CD63 captures EVs and immobilizes it on the electrode, and then the aptamer binding to EGFR contacts the EVs, which results in a change in redox current, due to the proximity of the reporter molecule to the electrode surface decreases electron efficiency. Continuous monitoring of tumor-derived EVs revealed significant variations in EVs concentrations across different tumor stages, which exhibited a strong correlation with tumor volume. This flexible microneedle sensor offers the advantages of selectivity, biocompatibility, and analytical performance, presenting a promising approach for tumor monitoring in vivo .
研究领域:
生物传感器
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纳米技术
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癌症研究
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分子诊断学
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生物医学工程
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.7
Jirui Wei,Xiaozheng He,Tingting Shi,Xiayu Jin,Jun Huang,Qingyao Du,Junda Huang,Tao Li,Xunjie Xie,Yuxin Huang,Chengtao Nie,Yiqi Fan,Xixiao Yang,Luyao Song,Waijiao Tang
Epidemiological studies indicate that Metabolic Associated Fatty Liver Disease (MAFLD) has become the most prevalent chronic liver disease globally. Identifying bioactive molecules from natural plants that can prevent and ameliorate MAFLD is an effective approach to discovering new MAFLD therapeutics. Liupao tea possesses antioxidant and metabolic regulatory properties. This study aimed to identify the active components of Liupao tea polyphenol extract (PLE), and its potential targets and mechanisms of action in the prevention of MAFLD. We performed experiments on MAFLD mice to establish the prevention efficacy of PLE against MAFLD and determine its optimal dosage. Furthermore, network pharmacology, molecular docking, and SPR were performed to predict that PLE’s targets for preventing MAFLD concentrate on the hepatic EGFR target. Knockout of EGFR in hepatocytes attenuated the effects of PLE. These findings indicate that PLE inhibits lipid accumulation by downregulating the EGFR/pEGFR-AKT/pAKT-SREBP-1-ACC1 pathway through binding to the EGFR receptor, thereby preventing MAFLD.
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产品关联
DOI
PubMed
高影响因子
BRITISH JOURNAL OF CANCER
·
2026
·
IF 7.8
Zhao Kun,Zhang Jian,Wang Ran,Wang Bin,Ye Dongfan,Huang XiaoOu,Qiu Lingxiao,Duan Yi,Xu Zhi
Background EGFR-tyrosine kinase inhibitors (EGFR-TKIs) prolong the survival of patients with non-small cell lung cancer (NSCLC); however, drug resistance limits their long-term efficacy. The role of STAT3 signaling in EGFR-TKI resistance is not completely understood. Methods Using immunohistochemistry, we assessed changes in STAT3 phosphorylation levels in NSCLC before and after EGFR-TKIs treatment. Through gene editing and transcriptome sequencing experiments, we investigated the mechanism by which STAT3 signaling mediates drug resistance. We conducted cell proliferation and nude mice tumorigenesis experiments to verify whether STAT3 inhibitors enhanced the anti-tumor effect of EGFR-TKIs on NSCLC. Results We found that inhibition of the MAPK pathway by EGFR-TKIs triggers the rapid activation of STAT3 in NSCLC. RNA-seq analysis and cellular experiments confirmed that STAT3 regulates the expression of stemness markers, which contribute to drug resistance. Cancer stemness maintenance depends on telomerase. We found that STAT3 also mediates NSCLC resistance by regulating telomerase expression. Finally, we demonstrated in both cellular and animal models that icaritin, an anti-hepatocellular carcinoma agent, significantly potentiates the anti-tumor efficacy of EGFR-TKIs against NSCLC by inhibiting STAT3 activation. Conclusions The combination of EGFR-TKIs and STAT3 inhibitors has the potential to be a better therapeutic strategy for EGFR-mutant NSCLC than EGFR-TKI monotherapy. The alternative text for this image may have been generated using AI.
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DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Gen Li,Chunxiu Cai,Ning Zhang,Zijia Wang,Mingzhe Zhang,Quan Liu,Siyu Chen,Yanfei Shang,Chengqing Zhao,Shenzhen Ren,Hailong An
The calcium-activated chloride channel TMEM16A is frequently overexpressed in breast cancer, establishing a reciprocal activation loop with EGFR signaling pathways that play a crucial role in the proliferation of breast cancer. Consequently, the simultaneous targeting of TMEM16A and EGFR may be a promising, yet underexplored, therapeutic strategy for breast cancer. Herein, we developed a carrier-free polyphenol nanonetwork (PFGH) using procyanidin (PC), a natural polyphenolic TMEM16A inhibitor, via coordination with Fe 3+ , for co-delivering PC and gefitinib (Gef), an EGFR inhibitor. The resulting nanosystem, eliminating the requirement for additional nanocarriers, exhibited remarkable photothermal properties, pH-responsive drug release, and CD44-mediated tumor targeting. Functional assays confirmed that PFGH, under NIR irradiation, potently inhibited TMEM16A channel currents and exhibited superior antiproliferative effects compared to free PC, Gef, or their combination. RNA sequencing analysis confirmed the transcriptomic alterations in apoptosis, cell proliferation, and cancer-related pathways induced by the PFGH. In vivo studies further demonstrated that PFGH augments tumor-targeted combinatorial therapy, leveraging its photothermal properties, targeted co-delivery, and loop-suppressing activity. For the first time, our work presents a carrier-free polyphenol nanonetwork specifically engineered to co-target the TMEM16A-EGFR mutual activation loop, offering a novel, synergistic therapeutic approach for breast cancer.
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产品关联
DOI
PubMed
高影响因子
NEUROPSYCHOBIOLOGY
·
2023
·
IF 3.2
Cao Ting,Wang LiWei,Jiao ShiMeng,Chen Hui,Lin ChenQuan,Zhang BiKui,Cai HuaLin
Introduction: Progesterone receptor component 1 (PGRMC1) has been identified as a potential target in atypical antipsychotic drug-induced metabolic disturbances as well as neuroprotection in the central nervous system. In our study, we aimed to figure out the essential role of PGRMC1 signaling pathway underlying clozapine-induced cognitive impairment. Methods: In male SD rats, we utilized recombinant adeno-associated viruses (BBB 2.0) and the specific inhibitor of PGRMC1 (AG205) to regulate the expression of PGRMC1 in the brain, with a special focus on the hippocampus. Treatments of clozapine and AG205 were conducted for 28 days, and subsequent behavioral tests including modified elevated plus maze and Morris water maze were conducted to evaluate the cognitive performance. Hippocampal protein expressions were measured by Western blotting. Results: Our study showed that long-term clozapine administration led to cognitive impairment as confirmed by behavioral tests as well as histopathological examination in the hippocampus. Clozapine inhibited neural survival through the PGRMC1/EGFR/GLP1R-PI3K-Akt signaling pathway, leading to a decrease in the downstream survival factor, brain-derived neurotrophic factor (BDNF), and simultaneously promoted neural apoptosis in the rat hippocampus. Intriguingly, by targeting at the hippocampal PGRMC1, we found that inhibiting PGRMC1 mimics, while its upregulation notably mitigates clozapine-induced cognitive impairment through PGRMC1 and its downstream signaling pathways. Conclusion: PGRMC1-overexpression could protect hippocampus-dependent cognitive impairment induced by clozapine. This effect appears to arise, in part, from the upregulated expression of PGRMC1/EGFR/GLP1R and the activation of downstream PI3K-Akt-BDNF and caspase-3 signaling pathways
研究领域:
神经科学
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药理学
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行为科学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Jia-Hua Zou,Li-Li Chen,Yong-Guo Hu,Dong Zhou,Yong Li,Bin Zhang,Xin-Yue Xu,Bo Liu,Jin-Xuan Fan,Yuan-Di Zhao
Accurate tumor detection is crucial for the early discovery and subsequent treatment of small neoplastic foci. Molecular imaging, which combines non-invasiveness, high specificity, and strong sensitivity, excels in diagnosing early tumors and stands out among tumor diagnosis methods. Here, we introduced a dual-modal imaging probe capable of actively targeting tumor cells, suitable for both near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI). Dendritic mesoporous silica was used as a carrier for the probe, encapsulating Ag2S quantum dots (QDs) for NIR fluorescence imaging. Additionally, the probe conjugated the MRI contrast agent Gd-DOTA and cetuximab, which targeted EGFR on the tumor cell membrane surface, to achieve dual-modal imaging in the tumor area. This strategy provided a methodology for the accurate diagnosis of early-stage tumor lesions and guides precise lesion resection during surgery, offering significant potential for clinical application.
研究领域:
生物医学工程
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分子成像
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癌症诊断
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纳米技术
✓ 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）