ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Weiwei Zeng,Zhuoyao Wu,Yan Xu,Weitao Yang,Bingbo Zhang
Molecular magnetic resonance imaging (mMRI) of biomarkers is essential for accurate cancer detection in precision medicine. However, the current clinically used contrast agents provide structural magnetic resonance imaging (sMRI) information only and rarely provide mMRI information. Here, a tumor-specific furin-catalyzed nanoprobe (NP) was reported for differential diagnosis of malignant breast cancers (BCs) in vivo. This NP with a compact structure of Fe3O4@Gd-DOTA NPs (FFG NPs) contains an “always-on” T2-weighted MR signal provided by the magnetic Fe3O4 core and a furin-catalyzed enhanced T1-weighted MR signal provided by the Gd-DOTA moiety. The FFG NPs were found to produce an activated T1 signal in the presence of furin catalysis and an “always-on” T2 signal, providing mMRI and sMRI information simultaneously. Ratiometric mMRI:sMRI intensity can be used for differential diagnosis of malignant BCs MDA-MB-231 and MCF-7, where the furin levels relatively differ. The proposed probe not only provides structural imaging but also enables real-time molecular differential visualization of BC through enzymatic activities of cancer tissues.
研究领域:
医学影像学
·
肿瘤学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2022
·Vol. 101
·期 3
·550-567
·
IF 2.873
Wenlin Lu,Xuhui Liu,Linghui Zhao,Shirong Yan,Qingyun Song,Cao Zou,Xun Li
Heart failure (HF) is often the inevitable manifestation of myocardial ischemia. Hypoxia can induce cardiomyocytes to express many microRNAs (miRNAs), which are highly expressed in exosomes. In addition, miR-22-3p is a marker in heart failure. Therefore, miR-22-3p was taken as the research object to explore its role and mechanism in HF. HF differentially expressed miRNAs were screened by bioinformatic analysis. The HF rats model was constructed and identified by detecting serum brain natriuretic peptide (BNP) and ultrasound analysis [left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS)]. The extracted exosomes were identified by transmission electron microscopy, and Western blot was used to detect the expressions of Tsg101 and CD63. Quantitative real-time polymerase chain reaction detected miR-22-3p expression in serum, exosomes, and serum without exosomes, while the cardiomyocytes cytotoxicity was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and PKH26 staining. After overexpressing/silencing miR-22-3p in cells, cell viability, apoptosis, and apoptosis-associated markers were detected. Bioinformatic analysis screened the target gene of miR-22-3p, which was verified by dual-luciferase assay. Regulation of miR-22-3p on FURIN was measured by rescue tests. In vivo experiments were verified the above results. MiR-22-3p was identified as the research object. BNP was increased in the model group, while LVEF and LVFS were decreased. MiR-22-3p was overexpressed in HF-treated serum and exosomes. Normal exosomes did not affect cardiomyocyte function, while high concentrations of HF-treated exosomes were cytotoxic. By regulating apoptosis-related genes, overexpressed miR-22-3p inhibited cell activity and promoted cell apoptosis. Silenced miR-22-3p with opposite effects counteracted effects of HF-treated exosomes. FURIN, target gene of miR-22-3p, was negatively regulated by miR-22-3p, while overexpressed FURIN promoted cell activity and inhibited apoptosis. In vivo research was consistent with the results of cell experiments. By regulating FURIN, miR-22-3p in exosomes increases the risk of HF damage.
研究领域:
心脏病学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Bioactive Materials
·
2020
·
IF 8.724
Yichuan Pang,Li Su,Yao Fu,Fan Jia,Chenxi Zhang,Xiankun Cao,Wenxin He,Xueqian Kong,Jiake Xu,Jie Zhao,An Qin
Breast cancer bone metastasis poses significant challenge for therapeutic strategies. Inside the metastatic environment, osteoclasts and tumor cells interact synergistically to promote cancer progression. In this study, the proprotein convertase furin is targeted due to its critical roles in both tumor cell invasion and osteoclast function. Importantly, the furin inhibitor is specifically delivered by bone targeting superparamagnetic iron oxide (SPIO) nanoparticles. Our in vitro and in vivo data demonstrate that this system can effectively inhibit both osteoclastic bone resorption and breast cancer invastion, leading to alleviated osteolysis. Therefore, the bone targeting & furin inhibition nanoparticle system is a promising therapeutic and diagnostic strategy for breast cancer bone metastasis.
研究领域:
肿瘤学
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纳米技术
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生物材料
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癌症转移
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DOI
PubMed
高影响因子
Oncology Letters
·
2017
·Vol. 15
·期 3
·3192-3196
·
IF 1.39
Meng Zhou,Youli Zhang,Hong Wei,Junbo He,Dawei Wang,Baoding Chen,Jian Zeng,Aihua Gong,Min Xu
Hexa-D-arginine (D6R), an inhibitor of furin, has potential therapeutic applications in different types of human tumor. However, the function of D6R in targeting pancreatic cancer cells remains to be elucidated. In the present study, the proliferation, invasion and migration abilities of SW1990 and PaTu8988 cells were examined using a Cell Counting Kit‑8, and Transwell and wound healing assays. Subsequently, the expression of proteins associated with epithelial‑mesenchymal transition (EMT) and the Hippo‑yes‑associated protein (YAP) pathway were detected using western blot analysis. It was revealed that D6R significantly inhibited the proliferation, migration and invasion abilities of SW1990 and PaTu8988 cells. Additionally, D6R led to the upregulation of E‑cadherin (an epithelial marker), and the downregulation of N‑cadherin and vimentin (mesenchymal markers) in SW1990 and PaTu8988 cells. Furthermore, the results of the present study revealed that D6R significantly affected the YAP phosphorylation level and the total YAP protein level, indicating that D6R was functionally involved in the Hippo‑YAP signaling pathway. It has been suggested that D6R‑suppressed EMT in SW1990 and PaTu8988 cells may occur via the Hippo‑YAP pathway and that it may be a feasible drug to ameliorate the malignant phenotype of SW1990 and PaTu8988 cells.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
REPRODUCTIVE TOXICOLOGY
·
2021
·
IF 3.143
Jiadong Chen,Lian Kang,Junke Wang,Yuhao Wu,Lindong Han,Xiangqin Zheng,Yuexin Wei,Tianxin Zhao,Lianju Shen,Chunlan Long,Guanghui Wei,Shengde Wu
Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor that accumulates in organisms in various ways and induces male reproductive system disorders. In this study, we established a testicular injury model by gavage with different concentrations of DEHP. The testes were then collected for RNA sequencing (RNA-seq), and the results were analyzed by bioinformatics and verified by experiments. Our research results show that different concentrations of DEHP interfere with testicular development differently. Weighted gene coexpression network analysis (WGCNA) generated sixteen modules and identified the turquoise module as key. Then, estrogen receptor 1 (ESR1), filamin A (Flna) and Furin were identified as hub genes. qPCR and immunohistochemistry results revealed that all three hub genes were upregulated. We detected the locations of these genes by immunohistochemistry. ESR1 was mainly located in Leydig cells; Flna immunostaining is observed in the Leydig and some germ cells and Furin staining was seen in almost all types of testicular cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed enrichment mainly in MAPK signaling pathways, p53 signaling pathways, HIF-1 signaling pathways, protein processing in the endoplasmic reticulum, apoptosis, the cell cycle, RNA degradation, etc. This is the first study using WGCNA to investigate the mechanism of DEHP-induced injury in the prepubertal testis, providing new research angles to further understand the mechanism of DEHP-induced injury in the prepubertal testis.
研究领域:
毒理学
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生殖生物学
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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
BIOCHEMICAL GENETICS
·
2025
·
IF 1.6
Tang Zhiqi,Nong Jiacong,Qiu Xue,Huang Junwen,Feng Xueyi,Tu Guangpeng,Li Lang
Acute myocardial infarction (AMI) continues to pose a substantial risk to human lives worldwide. Endoplasmic reticulum stress (ERS) is increasingly recognized as one of the potential mechanisms of myocardial injury following AMI. The primary goal of this study is to investigate the correlation between ERS and AMI through machine learning-based bioinformatics analysis, explore key genes, and conduct in vivo and in vitro experimental validation. We performed differential analysis and Weighted Gene Co-expression Network Analysis (WGCNA) on gene expression data from the GEO database (GSE62646). The intersection with ERS-related genes (ERSRGs) was taken to obtain AMI-ERS-related genes (MIEGs), and machine learning algorithms were further used to identify key genes (Hubs) from the MIEGs. The validation set GSE59867 was used to assess the expression levels and predictive capabilities of the Hubs for AMI. An AMI rat model was established to detect the mRNA and protein expression levels of the Hubs. The protein inhibitor of the key gene FURIN was used to treat H9C2 cells under oxygen–glucose deprivation (OGD) to explore the effects of FURIN on ERS and apoptosis. Bioinformatics analysis identified 27 MIEGs, and machine learning further determined 5 Hubs highly associated with AMI and ERS: RELA, FURIN, ERGIC3, TPP1, and BGLAP. The expression of these Hubs was significantly elevated in AMI patients within both the training and validation sets, and the area under the curve (AUC) indicated good diagnostic value. Our experiments confirmed that the mRNA levels of Furin and RelA were significantly elevated in AMI rats. Furin protein was increased in AMI rats and OGD H9C2. Furin inhibitor could alleviate OGD-induced ERS and apoptosis in H9C2. Our study demonstrates that Hubs play a pivotal role in myocardial infarction. Notably, Furin and its mediated ERS and apoptosis are significant in the pathogenesis of AMI, potentially serving as target for AMI diagnosis and treatment.
研究领域:
医学
·
生物信息学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2026
·
IF 5.2
Ziyi Xu,Guangzhao Lu,Xueli Jia,Min Zhu,Junjie Hua,Li Fan,Pei Chen,Huan Wang,Ying Lu,He Zhang
Multidrug resistance (MDR) and immunosuppression remain critical challenges in breast cancer therapy. Here, we report a size-tunable gold nanoparticle-based drug delivery system (AuNPs-DOX-RK&CABT) integrating chemotherapy, MDR reversal and macrophage repolarization. The dual-component system triggered furin-responsive click condensation reactions in tumors, inducing gold nanoparticles (AuNPs) aggregation to enhance tumor retention and intracellular acid-responsive doxorubicin (DOX) release. By inhibiting P-glycoprotein-mediated drug efflux and autophagy, the system overcame MDR while repolarizing M2-like tumor-associated macrophages (TAMs) to pro-inflammatory M1 phenotypes. In vivo studies in MCF-7/ADR tumor models demonstrated that AuNPs-DOX-RK&CABT significantly suppressed tumor growth, induced extensive necrosis/apoptosis, and modulated the immune microenvironment. This chemo-immunotherapeutic strategy integrated acid-responsive drug release, MDR reversal, and immune microenvironment modulation, offering a promising approach for MDR breast cancer treatment. Download: Download high-res image (468KB) Download: Download full-size image
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DOI
高影响因子
ADVANCED MATERIALS
·
2021
·Vol. 33
·期 45
·2104615
·
IF 30.849
Hui Jia,Defang Ding,Jingjing Hu,Jun Dai,Juliang Yang,Guogang Li,Xiaoding Lou,Fan Xia
Biochemical sensing probes based on aggregation-induced-emission luminogens (AIEgens) are widely used in biological imaging and therapy, chemical sensing, and material sciences. However, it is still a great challenge to quantify the targets through fluorescence intensity of AIEgen probes due to their undesirable aggregations. Here, a PyTPA-ZGO probe with three lifetime signals for precise quantification of furin is constructed: the lifetime signal 1 and signal 2 comes from AIEgen PyTPA-P (τ Pn ) and inorganic nanoparticles Zn 2 GeO 4 :Mn 2+ -NH 2 (τ Zn ), respectively, while the lifetime signal 3 is marked as the composite dual-lifetime signal (CDLS n , C D L S n = τ Z n τ P n ). In contrast, the fluorescence intensity signal of PyTPA-P shows defectively quantitative performance. Furthermore, it is found that the CDLS n exhibits higher significant differences than the two other lifetime signals (τ Pn and τ Zn ) thanks to its wide range between the maximum and minimum signal values and small standard deviation. Therefore, CDLS n is further used to accurately identify cell subtypes based on the specific concentration of furin in each subtype. The lifetime criterion can realize precise quantification, and it should be a promising direction of AIEgen-based quantitative analysis in the future.
研究领域:
生物成像
·
化学传感
·
材料科学
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DOI
PubMed
高影响因子
DRUG DELIVERY
·
2020
·
IF 4.902
Yunyan Chen,Mengfei Guo,Ding Qu,Yuping Liu,Jian Guo,Yan Chen
The accumulation and penetration of antitumor drugs in tumor tissues are directly related to their antitumor effects. The particle size of the nanodrug delivery system is one of the most important factors for the accumulation and penetration of antitumor drugs within tumor tissues. Generally, nanodelivery systems of intermediate size (100–120 nm) are capable of efficient accumulation owing to prolonged circulation and enhanced permeability and retention (EPR) effect; however, smaller ones (20–40 nm) are effective for deep penetration within tumor tissue. Currently a conventional drug delivery system cannot possess two types of optimal sizes, simultaneously. To solve this and to enhance cervical cancer treatment, a furin-responsive triterpenine-based liposomal complex (PEGcleavable Tf-CTM/L), with Tf-CTM (transferrin-modified tripterine-loaded coix seed oil microemulsion) in core, coated with a thermo-sensitive lipid and a kind of PEG shell modified with a furin-cleavable peptide was developed to improve tumor-specific accumulation and penetration. Herein, PEGcleavable Tf-CTM/L was capable of efficient accumulation because of EPR effect. The PEG shells could timely detach under stimulation of overexpressed furin protein to solve the problem of the steric hindrance dilemma. The small-sized Tf-CTM released under stimulation of tumor microthermal environment in cervical cancer, which was efficient with regards to deep penetration at tumor sites. Notably, compared to the use of triterpenine alone, PEGcleavable Tf-CTM/L promoted anticervical efficacy and displayed diminished systemic toxicity by efficient accumulation and deep penetration of antitumor drugs within tumor tissues. Our study provides a new strategy, and holds promising potential for anticervical cancer treatment.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
GLYCOCONJUGATE JOURNAL
·
2021
·Vol. 39
·期 3
·315-325
·
IF 2.916
Zeng Jiaxin,Meng Yuan,Chen Shi-Yi,Zhao Gaofeng,Wang Lianchun,Zhang En-Xin,Qiu Hong
Furin is one of the nine-member proprotein convertase family. Furin cleaves proteins with polybasic residues, which includes many viral glycoproteins such as SARS-Cov-2 spike protein. The cleavage is required for the activation of the proteins. Currently, the mechanisms that regulate Furin activity remain largely unknown. Here we demonstrated that Furin is a novel heparin/heparan sulfate binding protein by the use of biochemical and genetic assays. The K D is 9.78 nM based on the biolayer interferometry assay. Moreover, we found that sulfation degree, site-specific sulfation (N-sulfation and 3-O-sulfation), and iduronic acid are the major structural determinants for the binding. Furthermore, we found that heparin inhibits the enzymatic activity of Furin when pre-mixes heparin with either Furin or Furin substrate. We also found that the Furin binds with cells of different origin and the binding with the cells of lung origin is the strongest one. These data could advance our understanding of the working mechanism of Furin and will benefit the Furin based drug discovery such as inhibitors targeting the interaction between heparan sulfate and Furin for inhibition of viral infection.
研究领域:
分子生物学
·
病毒学
·
药理学
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产品关联
DOI
PubMed
高影响因子
CHEMBIOCHEM
·
2018
·Vol. 19
·期 10
·1060-1065
·
IF 2.774
Xueyu Zhao,Gaochao Lv,Ying Peng,Qingzhu Liu,Xi Li,Shanshan Wang,Ke Li,Ling Qiu,Jianguo Lin
Graphical Active duty : An activatable fluorescent probe consisting of a peptide, Arg-Val-Arg-Arg (RVRR), and an aminoluciferin fluorophore is designed and prepared for the responsive and activatable detection of furin activity in living cells. This probe is shown to have “off–on” florescence properties, and in the presence of furin in vitro, its fluorescence intensity is increased by a factor of ≈3.58. Furin, a protein convertase, plays a crucial role in the progression of tumors. In this work, a new fluorescent probe consisting of a peptide, Arg-Val-Arg-Arg (RVRR), and an aminoluciferin fluorophore was designed and prepared for the responsive and activatable detection of furin activity in vitro and in living cells. We demonstrated that this probe could be responsive toward furin with an “off–on” florescence signal and generated an approximately 3.58-fold enhancement in the fluorescence intensity in vitro. Fluorescence imaging in MDA-MB-468 and LoVo cells showed that the probe could be cleaved by overexpressed furin with fluorescence turn-on in MDA-MB-468 cells, and this probe was also found to be capable of discriminating between furin-overexpressing and furin-deficient cell lines. Our research indicates that this probe has great potential for the detection of furin activity in living cells.
研究领域:
生物化学
·
分子生物学
·
癌症研究
·
细胞生物学
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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）