Cells
·
2024
·Vol. 13
·期 3
·206
·
IF 5.1
Meng-Yuan Li,Ying Wang,Ying Wu,Xu-Yu Zhao,Zhen-Shan Yang,Bo Li,Si-Ting Chen,Yu-Ying He,Zeng-Ming Yang
(1) Background: Inflammatory responses are implicated in embryo implantation, decidualization, pregnancy maintenance and labor. Both embryo implantation and decidualization are essential to successful pregnancy in rodents and primates. S100A6 is involved in inflammation, tumor development, apoptosis and calcium homeostasis. S100A6 is strongly expressed in mouse decidua, but the underlying mechanisms of how S100A6 regulates implantation and decidualization are poorly defined. (2) Methods: Mouse endometrial stromal and epithelial cells are isolated from day 4 pseudopregnant mouse uteri. Both immunofluorescence and Western blotting are used to analyze the expression and localization of proteins. The molecular mechanism is verified in vitro by Western blotting and the quantitative polymerase chain reaction. (3) Results: From days 4 to 8 of pregnancy, S100A6 is specifically expressed in mouse subluminal stromal cells. Blastocyst-derived lactic acid induces AA secretion by activating the luminal epithelial p-cPLA2. The epithelial AA induces stromal S100A6 expression through the COX2/PGI2/PPAR δ pathway. Progesterone regulates S100A6 expression through the progesterone receptor (PR). S100A6/RAGE signaling can regulate decidualization via EGFR/ERK1/2 in vitro. (4) Conclusions: S100A6, as an inflammatory mediator, is important for mouse implantation and decidualization.Keywords:decidualization;implantation;S100A6;RAGE;inflammation
研究领域:
生殖生物学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
Journal of Gastrointestinal Oncology
·
2021
·
IF 2.892
Linghui Kong,Qun Zhang,Jialei Mao,Lei Cheng,Xiao Shi,Lixia Yu,Jing Hu,Mi Yang,Li Li,Baorui Liu,Xiaoping Qian
Background Epidermal growth factor receptor (EGFR) and its downstream Ras-mitogen-activated protein kinase kinase (MAPKK, MEK)-extracellular regulated protein kinase (ERK) signaling pathway and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling pathway play important roles in the pathogenesis of colorectal cancer (CRC). The combination therapy of anti-EGFR and anti-mTOR needs to be explored. Methods Here we combined the anti-EGFR monoclonal antibody cetuximab (CTX) with the mTOR inhibitor PP242 in CRC cell lines and mouse xenograft models and discussed the changes of EGFR downstream signaling pathways of CRC cell lines. Results In HT-29 cells and Caco-2 cells, combined application of CTX and PP242 significantly inhibited the proliferation of CRC cells in vivo and in vitro. In BRAF wild-type Caco-2 cells, combined application of CTX and PP242 inhibited the activation of the EGFR and its downstream signaling pathways. Conclusions Our research further demonstrates the effectiveness of the combined application of CTX and PP242 in inhibiting CRC cell lines from the perspective of cell proliferation, cell cycle, apoptosis, and mouse xenografts. We revealed that the combined application of CTX and PP242 can inhibit tumor growth and proliferation by inhibiting the phosphorylation of key molecules in EGFR downstream MEK-ERK and MEK 4/7 (MKK)-c-Jun N-terminal kinase (JNK) signaling pathways in BRAF wild-type CRC cells. In addition, we found that in BRAF mutant CRC cells, the monotherapy of PP242 resulted in negative feedback increased EGFR phosphorylation rates, accompanied by significant up-regulation of downstream MEK and ERK phosphorylation.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症治疗
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DOI
PubMed
高影响因子
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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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Peng Deng,Ge Sun,Jie Zhao,Kaitai Yao,Miaomiao Yuan,Lizeng Peng,Longfei Mao
Cervical cancer is one of the most important cause of cancer-related death and presents a major public health problem in many countries. To search for more novel antitumor agents against cervical cancer, 14 erlotinib-linked 1,2,3-triazole compounds were designed, synthesized, and evaluated for their anti-tumor activity. The compounds were confirmed by 1H NMR, 13C NMR, and high-resolution mass spectra (HR MS). Antitumor activity assay results indicated that six of those compounds have remarkable inhibitory activity against human cervical cancer HeLa cells in vitro, among which compound 4m was the most potent with IC50 of 3.79 μM, and compounds 4k, 4i, 4l, 4d, and 4n also demonstrated remarkable antitumor activity with IC50 of 3.79, 4.16, 4.36, 7.02, and 8.21 μM. We found three of the most potent compounds 4d, 4k, and 4l induced potent apoptosis and cell cycle arrest in HeLa cells, and compounds 4d and 4l significantly restrained the cell colony formation and showed moderate epidermal growth factor receptor (EGFR) inhibitory activity with IC50 of 13.01 and 1.76 μM. Therefore, these experiments indicate that these erlotinib-linked 1,2,3-triazole compounds are potential to act as effective anticancer agents against cervical cancer.Keywords: EGFR, erlotinib, 1,2,3-triazole, HeLa, antitumor activity
研究领域:
肿瘤学
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药物化学
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药理学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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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
·
2026
·
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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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
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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产品关联
DOI
PubMed
高影响因子
MOLECULAR DIVERSITY
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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
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2022
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IF 5.062
Yan Wang,Chen Zhang,Meng Xiao,Kumar Ganesan,Fei Gao,Qingqing Liu,Zhen Ye,Yue Sui,Feng Zhang,Kunhua Wei,Yaobin Wu,Jianmin Wu,Bing Du,Cong Xu,Yan Li,Peng Li,Jinming Zhang,Jianping Chen
Treatment of aggressive triple-negative breast cancer (TNBC) is still challenging. Isoliquiritigenin (ISL) is a water-insoluble bioactive compound possessing high anti-TNBC capacity with less toxicity. The present study aimed to develop a safe and effective oral drug delivery system to improve the oral efficacy of ISL for TNBC therapeutics. ISL-loaded zein phosphatidylcholine hybrid nanoparticles ( [email protected] NPs) were constructed by a one-step solvent evaporation method. Optimization and characterization of [email protected] NPs were performed. Cellular uptake in vitro and biodistribution of ZLH NPs in vivo were investigated. The pharmacokinetics of [email protected] NPs in terms of ISL content in the plasma, organs, and tumor tissues were validated, and the anti-TNBC efficacy was evaluated. Encapsulation efficiency (96.75 ± 1.41%) and drug loading efficiency (6.56 ± 0.83%) were found in [email protected] NPs. [email protected] NPs were able to enhance the absorption of ISL in the tumor sites. Moreover, the upregulation of p27 and downregulation of EGFR and CDK4 were observed in [email protected] NPs treated tumors. Collectively, oral intake of [email protected] NPs would be translated into a potential clinical therapy strategy against TNBC.
研究领域:
肿瘤学
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药剂学
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纳米技术
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分子生物学
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产品关联
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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DOI
PubMed
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.
研究领域:
药理学
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呼吸病学
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蛋白质组学
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传统中药
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产品关联
DOI
PubMed
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
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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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DOI
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