BIOSENSORS & BIOELECTRONICS
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2024
·
IF 10.7
Xiao Yang,Liangyi Zhao,Siyi Yang,Miao Tang,Huanbao Fa,Danqun Huo,Changjun Hou,Mei Yang
The detection of circulating tumor DNA (ctDNA), as a practical liquid biopsy technique, was of great significance for the study of cancer diagnosis and prognosis. However, reported methods for detection ctDNA still have some limitations, such as tedious process and high cost. In this study, CsPbBr 3 nanosheet (CsPbBr 3 NS) with high water stability was prepared by etching, and its fluorescence intensity could be stably stored for 1 year. The Ti 3 C 2 T x possessed high quenching efficiency for CsPbBr 3 NS and the HOMO-LUMO orbital study revealed that the PET mechanism was responsible for fluorescence quenching. And the Ti 3 C 2 T x showed stronger affinity towards single-stranded DNA (ssDNA), as compared with double-stranded DNA (dsDNA). The probe ssDNA could be adsorbed on the surface of Ti 3 C 2 T x through π-π stacking. After the targets were recognized by probe ssDNA to form dsDNA, its affinity with Ti 3 C 2 T x decreased and the active site of Ti 3 C 2 T x recovered, causing a high quenching efficiency on CsPbBr 3 NS. Based on this, a label-free fluorescent biosensor was designed for the sensitive detection of ctDNA ( EGFR 19 Dels for non-small cell lung cancer, NSCLC). Under the optimal experimental conditions, this biosensor exhibited a detection limit of 180 fM and a linear range of 50 pM–350 pM with amplification of magnetic beads through strand displacement reaction. In addition, this sensor was applied to the detection of ctDNA in serum samples and cells lysates. This method for ctDNA detection was expected to have great potential for biomarker detection in the field of liquid biopsy.
研究领域:
癌症诊断
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纳米技术
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生物传感器
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分子生物学
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生物医学工程
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DOI
PubMed
高影响因子
Nature Communications
·
2019
·Vol. 10
·期 1
·1-15
·
IF 11.878
Jin Nan,Bi Aiwei,Lan Xiaojing,Xu Jun,Wang Xiaomin,Liu Yingluo,Wang Ting,Tang Shuai,Zeng Hanlin,Chen Ziqi,Tan Minjia,Ai Jing,Xie Hua,Zhang Tao,Liu Dandan,Huang Ruimin,Song Yue,Leung Elaine Lai-Han,Yao Xiaojun,Ding Jian,Geng Meiyu,Lin Shu-Hai,Huang Min
One of the biggest hurdles for the development of metabolism-targeted therapies is to identify the responsive tumor subsets. However, the metabolic vulnerabilities for most human cancers remain unclear. Establishing the link between metabolic signatures and the oncogenic alterations of receptor tyrosine kinases (RTK), the most well-defined cancer genotypes, may precisely direct metabolic intervention to a broad patient population. By integrating metabolomics and transcriptomics, we herein show that oncogenic RTK activation causes distinct metabolic preference. Specifically, EGFR activation branches glycolysis to the serine synthesis for nucleotide biosynthesis and redox homeostasis, whereas FGFR activation recycles lactate to fuel oxidative phosphorylation for energy generation. Genetic alterations of EGFR and FGFR stratify the responsive tumors to pharmacological inhibitors that target serine synthesis and lactate fluxes, respectively. Together, this study provides the molecular link between cancer genotypes and metabolic dependency, providing basis for patient stratification in metabolism-targeted therapies.
研究领域:
肿瘤学
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代谢组学
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转录组学
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癌症生物学
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药理学
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DOI
PubMed
高影响因子
ACS Omega
·
2023
·
IF 4.1
Hao Wu,Xuefeng Ding,Yun Chen,Yanfei Cai,Zhaoqi Yang,Jian Jin
Antibody–drug conjugates (ADC) are an inevitable trend in the development of modern “precision medicine”. The goal of this work is to produce enzyme-responsive antibody nanoparticle-loaded medication (FMSN-Dox-H2-AE01) based on the EGFR antibody (AE01) and human serum albumin (HSA) shelled mesoporous silica nanoparticles. HSA and antibodies on the surface of the particlescan not only enhance the biocompatibility of the particle and avoid early drug leakage but also allow selective biodegradation triggered by matrix metalloproteinase-2 (MMP-2), which are overexpressed enzymes in some tumor tissues. The cytotoxicity test confirmed favorable safety and efficacy of the ADC. The mortality rate of cancer cells is about 85–90%. Moreover, the antibody nanoparticle-loaded drug showed distinguishing controlled release efficiency toward cancer cells induced by different levels of MMP-2 and pH. This enzyme-responsive FMSN-Dox-H2-AE01 offers a promising option for cancer therapy.
研究领域:
药学
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纳米技术
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癌症研究
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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
BIOCHEMICAL PHARMACOLOGY
·
2022
·
IF 6.1
Liangping Li,Pingping Li,Xuesong Ma,Shulan Zeng,Yan Peng,Guohai Zhang
p53 inactivation by disabling its function is a hallmark in lung carcinomas , emphasizing the significance of restoring p53 function as an attractive therapeutic strategy. However, the clinical efficacy of existing p53 activators is limited due to their inability to effectively activate p53 within the tumors. Here, we established a p53 activator screening assay in EGFR-driven lung cancer cells and identified a small molecular, MX-C4, as a promising candidate. Using high throughput compound screening and combination analyses, we found that MX-C4 effectively promoted the phosphorylation of p53 at serine-392 (s392). It exhibited potent antitumor activity in a variety of cancer cell lines, but only limited toxicity to NCI-H1299 (p53-null) and normal cell lines such as LX2 and HL-7702. Overexpression of p53 in NCI-H1299 cells by a p53 expressing virus vector sensitized cells to MX-C4 treatment, suggesting a p53-dependent anticancer activity. Furthermore, we demonstrated that MX-C4 bound to p53 and exerted its anticancer activity through cell cycle arrest at G2/M phase and apoptosis induction. Mechanistic study indicated that p53 activation regulated cell cycle and cell survival related targets at protein levels. Moreover, p53 activation raised phospho-p53 translocation to mitochondria and subsequently reorganized the Bcl-xl-Bak complex, thus conformationally activating Bak and inducing apoptosis. It is noteworthy that MX-C4 could effectively activate p53 within the tumors in EGFR-driven xenograft models, where tumor was significantly suppressed without obvious toxicity. Our study identified a promising candidate for lung cancer therapy by restoring p53 function.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2024
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IF 5.1
Xiaoqi Pang,Bingqian Zhou,Jingyi Wu,Qi Mo,Lijiao Yang,Tiaotiao Liu,Ge Jin,Lan Zhang,Xiang Liu,Xin Xu,Bangmao Wang,Hailong Cao
Consuming probiotic products is a solution that people are willing to choose to augment health. As one of the global health hazards, sleep deprivation (SD) can cause both physical and mental diseases. The present study investigated the protective effects of Lacticaseibacillus rhamnosus GG (LGG), a widely used probiotic, on SD mice model. Here, it’s shown that SD induced intestinal damage in mice, while LGG supplementation attenuated disruption of the intestinal barrier and enhanced antioxidant capacity. Microbiome analysis revealed that SD caused dysbiosis in the gut microbiota, characterized by increased levels of Clostridium XlVa, Alistipes, and Desulfovibrio, as well as decreased levels of Ruminococcus, which were partially ameliorated by LGG. Moreover, SD resulted in elevated pro-inflammatory cytokine concentrations in both the intestine and brain, while LGG provided protection in both organs. LGG supplementation significantly improved locomotor activity in SD mice. Although heat-killed LGG showed some protective effects in SD mice, its overall efficacy was inferior to live LGG. In terms of mechanism, it was found that AG1478, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, could diminish the protective effects of LGG. In conclusion, LGG demonstrated the ability to alleviate SD-induced intestinal barrier dysfunction through EGFR activation and alleviate neuroinflammation.
研究领域:
微生物学
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神经科学
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免疫学
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营养学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Liang Yu,Mingzu Zhang,Jinlin He,Xingwei Sun,Peihong Ni
ABSTRACT Anticancer drugs used for systemic chemotherapy often exhibit off-target toxicity and uncontrolled drug release due to their lack of targeting. To improve the bioavailability of drugs and reduce side effects, we have developed a mixed micelle of nanomedicine composed of two prodrugs with surface modified monoclonal antibody for cancer therapy. In this system, Nimotuzumab was used as targeting ligands of the mixed micelles (named as DCMMs) that is composed of polymer-doxorubicin prodrug (abbreviated as PEG- b -P(GMA- ss -DOX)) and maleimide polyethylene glycol-chlorin e6 (abbreviated as Mal-PEG-Ce6). The mixed micelles modified with Nimotuzumab (named as NTZ-DCMMs) bind to overexpressed EGFR receptors on Hepatoma-22 (H22) cells. Disulfide bonds in PEG- b -P(GMA- ss -DOX) are disrupted in tumor microenvironment, inducing the reduction-responsive release of DOX and leading to tumor cell apoptosis. Simultaneously, Chlorin e6 (Ce6) produced plenty of singlet oxygen ( 1 O 2 ) under laser irradiation to kill tumor cells. In vivo biological distribution and antineoplastic effect experiments demonstrate that NTZ-DCMMs enhanced drug enrichment at tumor sites through targeting function of antibody, dramatically suppressing tumor growth and mitigating cardiotoxicity of drugs. All results prove that NTZ-DCMMs have the ability to actively target H22 cells and quickly respond to tumor microenvironment, which is expected to become an intelligent and multifunctional drug delivery carrier for efficient chemotherapy and photodynamic therapy of hepatoma. Statement of significance Anticancer drugs used for systemic chemotherapy often exhibit off-target toxicity due to their lack of targeting. Therefore, it's necessary to develop effective, targeted, and collaborative treatment strategies. We construct a mixed micelle of nanomedicine based on two polymer prodrugs and modified with monoclonal antibody on surface for cancer therapy. Under the tumor cell microenvironment, the disulfide bonds of polymer- ss -DOX were broken, effectively triggering DOX release. The photosensitizer Ce6 could generate a large amount of ROS under light, which synergistically promotes tumor cell apoptosis. By coupling antibodies to the hydrophilic segments of polymer micelles, drugs can be specifically delivered. Compared with monotherapy, the combination of chemotherapy and photodynamic therapy can significantly enhance the therapeutic effect of liver cancer.
研究领域:
药学
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纳米技术
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癌症研究
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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
ANALYST
·
2019
·Vol. 144
·期 16
·4757-4771
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IF 4.019
Xiurui Zhu,Shisheng Su,Mingzhu Fu,Zhiyong Peng,Dong Wang,Xiao Rui,Fang Wang,Xiaobin Liu,Baoxia Liu,Lingxiang Zhu,Wenjun Yang,Na Gao,Guoliang Huang,Gaoshan Jing,Yong Guo
Droplet digital PCR (ddPCR) is a single-molecule amplification technology with broad applications in precision medicine and clinical diagnosis. Dual-fluorescence and four-cluster ddPCR (two/four-ddPCR) assay is an effective way to quantify copy numbers. Currently, two/four-ddPCR data are usually classified with manual thresholds. For clinical applications, automatic and accurate methods are required to avoid subjectivity in diagnosis. Although there are some automatic classification algorithms, their accuracy and robustness still need to be improved to meet the needs of clinical diagnosis. Therefore, a new method is in high demand to automatically classify two/four-ddPCR data in an accurate and robust way. Here, a novel density-watershed algorithm (DWA) method was developed for the accurate, automatic and unsupervised classification of two/four-ddPCR data. First, data gridding was applied to a scatter plot of the fluorescence signal intensity to calculate data densities. Based on the data densities, the watershed algorithm was used to divide the gridded scatter plot into isolated regions automatically. Next, an optimal cluster pattern was determined based on these isolated regions, and excess regions were merged. Finally, the two/four-ddPCR data were classified based on the merged regions, and DNA template copy numbers were calculated accordingly. Using the DWA method for the quantification of both wild types and mutants of epidermal growth factor receptor (EGFR) L858R and T790M, the classification results were highly consistent with expectations, and significantly better than commonly-used automatic algorithms for now. The computed template copy numbers scaled proportionally to the relative concentration of input templates (r2 > 0.998) in four orders of magnitude with a good reproducibility, and achieved a limit of detection over 40 times lower than the commonly-used automatic algorithms. Furthermore, the DWA method was validated on 254 clinical DNA samples derived from frozen tissues, formalin-fixed paraffin-embedded tissues and peripheral blood. In most cases, the DWA method derived accurate and valid classification results. This highly effective DWA method may be widely used for automatically classifying two/four-ddPCR data, and it will greatly promote the application of ddPCR in clinical diagnosis.
研究领域:
生物信息学
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分子生物学
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临床诊断
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精准医疗
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2024
·Vol. 43
·期 1
·1-20
·
IF 11.4
Xu Wenjing,Li Yingqiu,Liu Lumei,Xie Jing,Hu Zongren,Kuang Shida,Fu Xinying,Li Bonan,Sun Tiansong,Zhu Congxu,He Qinghu,Sheng Wen
Background Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa. Methods A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development. Results After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3 + CD8 + IFN-γ, CD3 + CD8 + Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2. Conclusions ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.
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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药理学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Ting-Ting He,Xin Li,Jie-Zhi Ma,Yuan Yang,Shiye Zhu,Jianhua Zeng,Lin Luo,Yu-Long Yin,Lin-Ying Cao
Triclocarban (TCC) and triclosan (TCS) have been detected ubiquitously in human body and evoked increasing concerns. This study aimed to reveal the induction risks of TCC and TCS on triple negative breast cancer through non-genomic GPER-mediated signaling pathways. Molecular simulation indicated that TCC exhibited higher GPER binding affinity than TCS theoretically. Calcium mobilization assay displayed that TCC/TCS activated GPER signaling pathway with the lowest observed effective concentrations (LOEC) of 10 nM/100 nM. TCC and TCS also upregulated MMP-2/9, EGFR, MAPK3 but downregulated MAPK8 via GPER-mediated signaling pathway. Proliferation assay showed that TCC/TCS induced 4 T1 breast cancer cells proliferation with the LOEC of 100 nM/1000 nM. Wound-healing and transwell assays showed that TCC/TCS promoted 4 T1 cells migration in a concentration-dependent manner with the LOEC of 10 nM. The effects of TCC on breast cancer cells proliferation and migration were stronger than TCS and both were regulated by GPER. TCC/TCS induced migratory effects were more significantly than proliferative effect. Mechanism study showed that TCC/TCS downregulated the expression of epithelial marker (E-cadherin) but upregulated mesenchymal markers (snail and N-cadherin), which was reversed by GPER inhibitor G15. These biomarkers results indicated that TCC/TCS-induced 4 T1 cells migration was a classic epithelial to mesenchymal transition mechanism regulated by GPER signaling pathway. Orthotopic tumor model verified that TCC promoted breast cancer in-situ tumor growth and distal tissue metastasis via GPER-mediated signaling pathway at human-exposure level of 10 mg/kg/d. TCC-induced tissue metastasis of breast cancer was more significantly than in-situ tumor growth. Overall, we demonstrated for the first time that TCC/TCS could activate the GPER signaling pathways to induce breast cancer progression.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Tiantian An,Zhaoyu Xu,Yang Yang,Xinhui Li,Shuaidong Chen,Xingmei Yang,Yi Man,Chen Hu,Yili Qu
This study investigates the role of γδ T cells in wound healing facilitated by an EGCG (Epigallocatechin gallate)-releasing nanofibrous scaffold with aligned topography (APEMS). Incorporating core-shell microcapsules for sustained EGCG release over 11 days, the biocompatible scaffold enhances γδ T cell activity to promote advanced wound repair. In a splinted wound excisional model in 6-8 weeks-old male C57BL/6J mice, APEMS significantly improved re-epithelialization and wound closure compared to a control scaffold (APS). Single-cell RNA sequencing revealed a marked increase in γδ T cell in the APEMS group, where γδ T cells accounted for 66.2% of the T cell population, compared to 33.8% in the APS group. Cellchat analysis identified the AREG-EGFR signaling axis as pivotal to γδ T cell-mediated wound repair. APEMS-induced γδ T cells secreted amphiregulin (AREG), which acted on keratinocytes and fibroblasts to enhance keratinocyte proliferation, migration, and fibroblast-driven extracellular matrix remodeling. In immunodeficient mice lacking mature γδ T cells (TCRδ-/-), wound healing was significantly impaired, characterized by delayed re-epithelialization, reduced neo-dermal thickness, and increased inflammation. Inhibition of AREG and EGFR function via monoclonal antibodies against AREG and EGFR antagonist Gefitinib similarly delayed wound healing, the therapeutic advantage of APEMS over APS was abolished, emphasizing its critical role in the process. These findings provide a framework for developing advanced wound management materials and highlight the therapeutic potential of targeting γδ T cells and AREG-EGFR signaling to enhance tissue regeneration.
研究领域:
生物材料
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免疫学
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组织工程
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再生医学
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药学
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细胞生物学
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皮肤科学
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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
Scientific Reports
·
2015
·Vol. 5
·期 1
·1-17
·
IF 5.578
Cao Wei,Liu Ying,Zhang Ran,Zhang Bo,Wang Teng,Zhu Xianbing,Mei Lin,Chen Hongbo,Zhang Hongling,Ming Pinghong,Huang Laiqiang
Tyrosine kinase inhibitors (TKIs) are mostly used in non-small cell lung cancer (NSCLC) treatment. Unfortunately, treatment with Gefitinib for a period of time will result in drug resistance and cause treatment failure in clinic. Therefore, exploring novel compounds to overcome this resistance is urgently required. Here we investigated the antitumor effect of homoharringtonine (HHT), a natural compound extracted from Cephalotaxus harringtonia , on Gefitinib-resistant NSCLC cell lines in vitro and in viv o. NCI-H1975 cells with EGFR T790M mutation are more sensitive to HHT treatment compared with that of A549 cells with wild type EGFR. HHT inhibited cells growth, cell viability and colony formation, as well as induced cell apoptosis through mitochondria pathway. Furthermore, we explored the mechanism of HHT inhibition on NSCLC cells. Higher level of interleukin-6 (IL-6) existed in lung cancer patients and mutant EGFR and TGFβ signal requires the upregulation of IL-6 through the gp130/JAK pathway to overactive STAT3, an oncogenic protein which has been considered as a potential target for cancer therapy. HHT reversiblely inhibited IL-6-induced STAT3 Tyrosine 705 phosphorylation and reduced anti-apoptotic proteins expression. Gefitinib-resistant NSCLC xenograft tests also confirmed the antitumor effect of HHT in vivo . Consequently, HHT has the potential in Gefitinib-resistant NSCLC treatment.
研究领域:
肿瘤学
·
药理学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
TALANTA
·
2021
·
IF 6.057
Xin Zhu,Zenghui Liu,Jinge Li,Zutian Li,Fuchun Si,Huaixia Yang,Jinming Kong
Exosomes, as a biomarker with enhancing tumor invasion and spread, play an essential role for lung cancer diagnosis, therapy, and prognosis. In this work, a novel electrochemical sensor was fabricated for detecting exosomes secreted by lung cancer cells based on polysaccharide-initiated ring-opening polymerization (ROP) and click polymerization. First, MPA formed a self-assembled monolayer on the gold electrode surface, and then anti-EGFR was immobilized on the electrode surface by amide bond. Subsequently, a lot of phosphate groups were introduced by the specific recognition between anti-EGFR and exosomes, then sodium alginate grafted Glycidyl propargyl ether (SA- g -GPE) prepared via ROP was attached to the exosomes through PO 4 3- Zr 4+ -COOH coordination bond. After that, click polymerization was initiated by alkyne groups on the SA- g -GPE polymerization chain to realize highly sensitive detection of A549 exosomes. Under the optimum conditions, the fabricated sensor showed a good linear relationship between the logarithm of exosomes concentration and peak current in the range of 5 × 10 3 - 5 × 10 9 particles/mL, and the limit of detection (LOD) was as low as 1.49 × 10 2 particles/mL. In addition, this method had the advantages of high specificity, anti-interference, high sensitivity, simplicity, rapidity and green economy, which proposed a novel avenue for the detection of exosomes, and also had potential applications in early cancer diagnosis and biomedicine.
研究领域:
生物标志物研究
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癌症诊断
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电化学
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聚合物科学
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生物医学工程
✓ 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）