JOURNAL OF BIOMATERIALS APPLICATIONS
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2024
·
IF 2.3
Guojie Lu,Huiling Zhong,Jianwei Gao,Yaosen Zhang
The long non-coding RNA HOTAIR and the Hedgehog-Gli1 signaling pathway are closely associated with tumor occurrence and drug resistance in various cancers. However, their specific roles in the development of EGFR-TKIs resistance in non-small cell carcinoma remain unclear. To address the issue of EGFR-TKIs resistance, this study utilized the electrospray method to prepare sodium alginate microspheres encapsulating HOTAIR siRNA (SA/HOTAIR siRNA) and investigated its effects on RNA interference (RNAi) in the gefitinib-resistant cell line PC9/GR. Furthermore, the study explored whether HOTAIR could modulate EGFR-TKIs resistance through the Hedgehog-GLi1 signaling pathway. The experimental results showed that sodium alginate (SA) microspheres demonstrated excellent biocompatibility with high encapsulation efficiency and drug-loading capacity, effectively enhancing the silencing efficiency of siRNA. HOTAIR siRNA significantly inhibited the proliferation, migration, and invasion abilities of PC9/GR cells while promoting apoptosis. Additionally, HOTAIR siRNA effectively suppressed tumor growth and downregulated the Hedgehog-GLi1 pathway and anti-apoptotic proteins, which were confirmed in animal experiments. Moreover, SA/HOTAIR siRNA exhibited superior inhibition of cellular and tumor functions compared to using HOTAIR siRNA alone. Clinical research findings indicated that monitoring the expression level of HOTAIR in the serum and urine samples of NSCLC patients before and after receiving EGFR-TKIs treatment can predict the efficacy of EGFR-TKIs to a certain extent. This study provided evidence that HOTAIR siRNA effectively mitigated the development of acquired resistance to EGFR-TKIs by inhibiting the Hedgehog-GLi1 pathway. Furthermore, it introduced a reliable and long-lasting drug delivery system for combating acquired resistance to EGFR-TKIs.
研究领域:
肿瘤学
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分子生物学
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药学
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癌症治疗
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2026
·
IF 6
Tianying Wang,Xinyi Zhang,Lingling Zhou,Kaichao Wen,Xiyu Yang,Yixian Li,Yongkang Mu,Xuan Liu,Qizhi Zhang
Epidermal growth factor receptor (EGFR) inhibitors frequently cause cutaneous toxicities that impair patients’ quality of life and may compromise treatment adherence. Although topical vitamin K1 (VK1) has shown therapeutic potential, its clinical efficacy remains inconsistent, largely due to poor distribution within pharmacologically relevant skin compartments, particularly the viable epidermis and pilosebaceous units. To address this, we developed a VK1-loaded liposome‑in‑hydrogel (VK1-Lipo-Gel) capable of sustaining intradermal drug residence while minimizing systemic exposure. Compared with the commercial VK1 cream, VK1-Lipo-Gel markedly prolonged VK1 retention in the skin. VK1 remained detectable in the viable epidermis–dermis (VED) for up to 36 h, yielding a C max of 1.64 ± 0.10 μg/cm 2 at 8 h and an AUC 0–36h of 33.16 ± 1.70 μg·h/cm 2 . Notably, the formulation promoted preferential localization within the VED and pilosebaceous units, with plasma VK1 levels below the LLOQ. More importantly, VK1‑Lipo‑Gel did not compromise the antitumor efficacy of erlotinib. In an erlotinib-induced skin toxicity model, by restoring EGFR–ERK signaling, VK1-Lipo-Gel more effectively reinforced epidermal barrier function, attenuated inflammatory responses, and ameliorated follicle‑associated alterations. These results demonstrate that optimizing intradermal retention and compartment‑specific distribution, rather than simply increasing transdermal flux, is a superior strategy for managing EGFR inhibitor-induced cutaneous toxicity, and support the translational potential of liposome‑hydrogel hybrids for topical drug delivery. Download: Download high-res image (202KB) Download: Download full-size image
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高影响因子
BIOSENSORS & BIOELECTRONICS
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2026
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IF 11.8
Yan Wang,Boya Xu,Zehan Zeng,Haixin Wang,Lin Shi,Wanting Liu,Yanyan Chen,Xuexian Deng,Jun Chen,Jin-Xiang Chen
Extracellular vesicle (EV)-based liquid biopsy holds great promise for glioma diagnosis, but its clinical translation remains hindered by inefficient isolation of disease-relevant EV subpopulations and insufficiently integrated signal validation. Herein, we develop a platform that integrates a bifunctional nanozyme system (phosphatase-like MOF and peroxidase-like Pt) with a CHA-CRISPR/Cas12a cascade, achieving selective isolation and ultrasensitive detection of EGFR-positive glioma-derived EVs. Defective UiO-66-NH 2 loaded with Pt nanoparticles and functionalized with EGFR aptamers (UiO@Pt@Apt) is immobilized on Hook strand-modified glass 96-well plates via Apt-Hook hybridization. Upon introduction of EGFR-positive EVs, they specifically bind to aptamers on UiO@Pt@Apt and induce the release of UiO@Pt@Apt-EV complexes through perturbation and destabilization of the Apt-Hook interface. After EV lysis, EV-derived miRNA-21 activates the CHA-CRISPR/Cas12a cascade to generate a fluorescent signal, while the nucleotide fragments produced by Cas12a trans-cleavage are proposed to be hydrolyzed by phosphatase-like defective UiO-66-NH 2 to generate PO 4 3− . The PO 4 3− may contribute to Pt-mediated TMB oxidation, thereby supporting colorimetric signal amplification. The platform achieved a colorimetric EV detection limit of 427 particles/μL after coupling with the CHA-CRISPR system, representing a 6.9-fold improvement over the UiO@Pt@Apt system alone, and enabled a miRNA-21 detection limit of 87.0 fM. In plasma samples from 25 glioma patients and 20 healthy donors, the combined readout achieved an AUC of 0.968, showing numerically better discriminatory performance than either single readout, although the improvement was not statistically significant by DeLong analysis. This work provides a promising strategy for EV-based glioma liquid biopsy and offers a potentially adaptable framework for cascade-coupled dual-signal biosensing.
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高影响因子
Oncology Letters
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2022
·Vol. 24
·期 5
·1-9
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IF 3.111
Yang Chen,Li Hou
It has previously been reported that human hepatocellular carcinoma‑related protein 1 (HCRP‑1), which is a tumor suppressor gene, and epidermal growth factor receptor (EGFR) are abnormally expressed in certain solid tumors. Therefore, in the present study, the expression patterns of HCRP‑1 in oral squamous cell carcinoma (OSCC) are discussed. Moreover, the present study investigated whether HCRP‑1 regulated EGFR expression levels and its downstream effectors to further determine the regulation of tumor cell behavior. Therefore, the expression levels of HCRP‑1 in normal oral epithelial and OSCC cells were determined, and the effects of HCRP‑1 overexpression on OSCC cell proliferation, migration and invasion were assessed. Moreover, the culture medium from the different groups of OSCC cells was separately supplemented into the human umbilical vein endothelial cell (HUVEC) cultures, and the migration and angiogenesis of the HUVECs were assessed. To determine the roles of EGFR/STAT3 in the regulation of HCRP‑1, EGF and colivelin, a STAT3 agonist, were used to treat CAL‑27 cells and their effects on the cells were assessed using the aforementioned functional experiments. The results demonstrated that HCRP‑1 expression levels were downregulated in OSCC cells and that HCRP‑1 overexpression could suppress OSCC cell proliferation, migration and invasion. Moreover, the culture medium from OSCC cells overexpressing HCRP‑1 facilitated the migration and angiogenesis of HUVECs. Furthermore, HCRP‑1 was demonstrated to function in cells by regulating the EGFR/STAT3 signaling pathway. In summary, the present study indicated that HCRP‑1 alleviated the malignant phenotype and angiogenesis of OSCC cells via the downregulation of the EGFR/STAT3 signaling pathway.
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高影响因子
MOLECULES
·
2021
·Vol. 26
·期 14
·4361
·
IF 4.412
Ya Wang,Xiao-Jing Shen,Fa-Wu Su,Yin-Rong Xie,Li-Xia Wang,Ning Zhang,Yi-Long Wu,Yun Niu,Dong-Ying Zhang,Cheng-Ting Zi,Xuan-Jun Wang,Jun Sheng
Lung cancer is one of the most commonly occurring cancer mortality worldwide. The epidermal growth factor receptor (EGFR) plays an important role in cellular functions and has become the new promising target. Natural products and their derivatives with various structures, unique biological activities, and specific selectivity have served as lead compounds for EGFR. D-glucose and EGCG were used as starting materials. A series of glucoside derivatives of EGCG (7–12) were synthesized and evaluated for their in vitro anticancer activity against five human cancer cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480. In addition, we investigated the structure-activity relationship and physicochemical property–activity relationship of EGCG derivatives. Compounds11and12showed better growth inhibition than others in four cancer cell lines (HL-60, SMMC-7721, A-549, and MCF), with IC50values in the range of 22.90–37.87 μM. Compounds11and12decreased phosphorylation of EGFR and downstream signaling protein, which also have more hydrophobic interactions than EGCG by docking study. The most active compounds11and12, both having perbutyrylated glucose residue, we found that perbutyrylation of the glucose residue leads to increased cytotoxic activity and suggested that their potential as anticancer agents for further development.Keywords:EGCG;synthesis;cytotoxicity;EGFR;molecular docking
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高影响因子
RSC Advances
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2019
·Vol. 9
·期 66
·38298-38308
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IF 3.049
Xiaojun Xu,Shu Xing,Mengjia Xu,Pan Fu,Tingting Gao,Xiaokang Zhang,Yang Zhao,Chao Zhao
Screening epidermal growth factor receptor (EGFR) mutations, especially deletions, is essential for diagnosis of non-small cell lung cancer (NSCLC) and also critical to inform treatment decisions for NSCLC patients. Here, we demonstrated a facile peptide nucleic acid (PNA) microarray-based fluorometric method for sensitive and specific detection of EGFR mutation, using rolling circle amplification (RCA), graphene oxide (GO), and a fluorescently-labeled detection probe (F-DP). First, the EGFR gene sequence was efficiently captured by the label-free PNA probe which was attached on the surface of a 96-well plate. And then, the EGFR mutation sequence was specifically amplified by RCA using the circular DNA, which was formed by the ligation of the padlock probe when hybridizing with the EGFR mutation, as a template. The single-stranded RCA product (RCAP) was then sensitively detected with the F-DP and GO system. This method has a detection limit of 0.3 pM for EGFR mutation and a high discrimination capability to target EGFR mutation against EGFR wildtype. The use of a PNA microarray and a fluorescence quenching platform make this system quite suitable for high-throughput analysis of EGFR mutations in resource-limited settings without the need of costly and cumbersome equipment. Furthermore, this detection system provides a novel way for the diagnosis of other diseases that are caused by gene deletion mutations.
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高影响因子
ACS Applied Materials & Interfaces
·
2025
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IF 8.2
Kaiyong Yang,Chunli Zhang,Zeyu Wang,Qiqing Huang,Jing Qian,Gaoyu Shi,Wenwen Sun,Jinqiu Wang,Yu Ji,Zhaorui Sun,Yanni Song,Xin Han
EGFR tyrosine kinase inhibitors (EGFR-TKIs) have garnered substantial clinical success in treating nonsmall cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. However, the inevitable emergence of drug resistance, frequently attributed to activation, mutation, or deletion of multiple signaling pathways, poses a significant challenge. Notably, the loss of PTEN protein expression has emerged as a pivotal mechanism fostering resistance in EGFR mutant lung cancers. Consequently, strategies aimed at upregulating PTEN expression hold great promise for restoring drug sensitivity. Leveraging the versatility, precision, and efficacy of nuclease-deactivated Cas9 (dCas9) as a transcriptional activator, we designed a CRISPR-dCas9 system to stimulate PTEN expression. To further enhance target specificity and drug delivery efficiency, we innovatively harnessed the tumor cell membrane (CCM) as a homologous targeting surface coating for our vector, thereby creating a targeted activation nanoplatform. Comprehensive in vitro and in vivo evaluations demonstrated that the synergistic interplay between gefitinib and the CRISPR-dCas9 system significantly enhanced drug sensitivity. The finding underscores the potential of our approach in addressing the issue of lung cancer resistance, offering a promising avenue for personalized and effective cancer therapies.
研究领域:
肿瘤学
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分子生物学
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基因治疗
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纳米医学
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PubMed
高影响因子
MOLECULAR DIVERSITY
·
2024
·Vol. 28
·期 6
·3713-3737
·
IF 3.9
Zhang Minjie,Chen Guifen,Chen Yafang,Sui Yi,Zhang Yan,Yang Wude,Yu Xiang
In order to develop new natural product-based anticancer agents, a series of 1,3,4-oxadiazole analogues based on petiolide A were prepared and evaluated for their anticancer activities by MTT method. The structures of all analogues were characterized by various spectral analyses, and B9 was further confirmed by X-ray crystallography. Among all the synthesized compounds, B1 displayed the most promising growth inhibitory effect on colon cancer cells (HCT116) with the IC 50 value of 8.53 μM. Flow cytometric analysis exhibited that B1 arrested the cell cycle at G2 phase and induced apoptosis. Additionally, network pharmacology analysis calculated that B1 might target several key proteins, including AKT serine/threonine kinase 1 (AKT1), SRC proto-oncogene, non-receptor tyrosine kinase (SRC) and epidermal growth factor receptor (EGFR). Furthermore, molecular docking study indicated that B1 had potentially high binding affinity to these three target proteins. Given these results, analogue B1 could be deeply developed as potential anticancer agents.
研究领域:
药物化学
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药理学
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肿瘤学
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化学生物学
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结构生物学
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DOI
高影响因子
RSC Advances
·
2026
·Vol. 16
·期 15
·13394
·
IF 6.1
Peng Ning,Fan Yang,Hongyi Cao,Bo Zhou
Sodium Danshensu (SDSS) shows potential in treating diabetic wounds (DWs) owing to its antioxidant, anti-inflammatory, and pro-angiogenesis effects. The specific pharmacological mechanisms of SDSS in achieving the above effects were evaluated. The potential targets of SDSS and DWs were obtained from online databases. Interaction networks were constructed using network pharmacology, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Combined with machine learning, the biological targets were evaluated and prioritized. A high-glucose-induced human umbilical vein endothelial cell (HUVEC) model was established for in vitro studies. A total of 126 shared targets of SDSS and DWs were selected, and the core targets included EGFR, CASP3, SRC, ESR1, JUN, NFKB1, IGF1R, ESR2, AR, and PPARG. KEGG enrichment analysis revealed significant enrichment of the PI3K-AKT signaling pathway ( P < 0.05). Machine learning indicated EGFR as a key target of SDSS in treating DWs. Findings from molecular docking and molecular dynamics simulation confirmed the stable combination of SDSS and EGFR. In vitro experiments indicated that SDSS may activate the PI3K-AKT pathway via EGFR targets, improve the mobility of high-glucose-induced HUVECs, and increase lumen formation (branch number). It promoted catalase production and inhibited the release of malondialdehyde and inflammatory factors including tumor necrosis factor-α and interleukin-6 (all P < 0.05). SDSS activates the PI3K-AKT pathway via EGFR, promotes endothelial cell migration and angiogenesis, and inhibits oxidative stress and the inflammatory response, highlighting its potential in treating DWs. Sodium Danshensu (SDSS) shows potential in treating diabetic wounds (DWs) owing to its antioxidant, anti-inflammatory, and pro-angiogenesis effects.
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高影响因子
Frontiers in Pharmacology
·
2019
·
IF 3.845
Ma Xiaoyao,Liu Aina,Liu Wenjuan,Wang Zhihua,Chang Nianwei,Li Suyun,Li Jiansheng,Hou Yuanyuan,Bai Gang
Chronic obstructive pulmonary disease (COPD) has been a major public health problem and is still a formidable challenge for clinicians. It is urgent to find new compounds for minimizing the risk of disease progression and exacerbation especially in the early phase of COPD. A traditional Chinese medicine (TCM) formula, Chuan Bei Pi Pa dropping pills (CBPP), was tested in this study to investigate its potential mechanisms in preventing the exacerbation of COPD. Phosphoproteomics analysis for a smog stimulated early stage COPD mice model was employed to detect the underlying molecular mechanisms of CBPP. In addition, protein–protein interaction (PPI) and bioinformatics analyses were included to analyze the key proteins and predict the key bioactive compounds. The results indicated that peiminine (PEI) target epidermal growth factor receptor (EGFR) prevented the exacerbation of COPD by inhibiting the EGFR signaling pathway, and ursolic acid (UA) can alleviate inflammation disorders via inhibition of CASP3 on mitogen-activated protein kinase (MAPK) signaling pathway. After in vivo and in vitro evaluations, we revealed that PEI from CBPP, as a lead compound, can improve lung function and alleviate pulmonary fibrosis by acting on the EGFR and MLC2 signaling pathways. Furthermore, the approach described here is an effective way to analyze and identify the bioactive ingredients from a mixture by functional proteomics analysis.
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高影响因子
Cancer Management and Research
·
2018
·
IF 3.702
Xuanxuan Dai,Junru Zhang,Guilong Guo,Yuepiao Cai,Ri Cui,Changtian Yin,Weidong Liu,Rajamanickam Vinothkumar,Tingting Zhang,Guang Liang,Xiaohua Zhang
Introduction Targeted therapies using epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR mutations, leading to the approval of gefitinib and erlotinib as standard first-line clinical treatment. Inevitably, a considerable proportion of patients develop resistance to EGFR-TKIs due to the acquisition of secondary mutations within EGFR. Therefore, alternative strategies to target NSCLC are desperately needed. Materials and methods In this study, we have evaluated the effect of a reactive oxygen species (ROS)-inducing agent WZ35, a mono-carbonyl analog of curcumin, to target an inherent biological property of cancer cells, increased oxidative stress. To study whether WZ35 can inhibit NSCLC tumorigenesis, we used gefitinib- and erlotinib-resistant cell line H1975. Results In this study, we show that WZ35 treatment dramatically decreases cell viability and induces apoptosis in H1975 cells through the generation of ROS. We also found that the antitumor activity of WZ35 involved ROS-mediated activation of the endoplasmic reticulum stress pathway and mitochondrial dysfunction. Furthermore, WZ35 significantly inhibited H1975 xenograft tumor growth through the inhibition of cell proliferation and induction of apoptosis. Discussion These findings show that WZ35 may be a promising candidate for the treatment of EGFR-TKI-resistant NSCLC.
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高影响因子
Cell Regeneration
·
2021
·Vol. 10
·期 1
·1-18
·
IF 0
Zhao Zixian,Wang Yujia,Wu Yingchuan,Li Dandan,Zhang Ting,Ma Yu,Teng Xiaoming,Zuo Wei
Information about the dynamic change and post-injury regeneration of cervical epithelium is relatively rare, even though it is tightly related to gynecologic malignancy. Here, using a feeder cell-based culturing system, we stably cloned mouse and human P63 and KRT5 expressing cells from the adult cervix as putative cervical stem/progenitor cells (CVSCs). When subjected to differentiation, the cultured cells gave rise to mature cervical epithelium by differentiating into squamous or glandular cells. The ability of endogenous mouse CVSCs to reconstitute cervical epithelium after injury was also evident from the genetic lineage tracing experiments. Single-cell transcriptomic analysis further classified the CVSCs into three subtypes and delineated their bi-lineage differentiation roadmap by pseudo-time analysis. We also tracked the real-time differentiation routes of two representing single CVSC lines in vitro and found that they recapitulated the predicted roadmap in pseudo-time analysis. Signaling pathways including Wnt, TGF-beta, Notch and EGFR were found to regulate the cervical epithelial hierarchy and implicated the different roles of distinct types of cells in tissue homeostasis and tumorigenesis. Collectively, the above data provide a cloning system to achieve stable in vitro culture of a bi-lineage stem/progenitor cell population in the cervix, which has profound implications for our understanding of the cervix stem/progenitor cell function in homeostasis, regeneration, and disease and could be helpful for developing stem cell-based therapies in future.
研究领域:
细胞生物学
·
干细胞研究
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癌症生物学
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再生医学
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