EMBO JOURNAL
·
2020
·Vol. 39
·期 5
·e101679
·
IF 9.889
Jun Wu,Wen-Jia Tian,Yang Liu,Huanhuan J Wang,Jiangli Zheng,Xin Wang,Han Pan,Ji Li,Junyu Luo,Xuerui Yang,Lester F Lau,H Troy Ghashghaei,Qin Shen
Adult neural stem cells (NSCs) reside in specialized niches, which hold a balanced number of NSCs, their progeny, and other cells. How niche capacity is regulated to contain a specific number of NSCs remains unclear. Here, we show that ependyma-derived matricellular protein CCN1 (cellular communication network factor 1) negatively regulates niche capacity and NSC number in the adult ventricular–subventricular zone (V-SVZ). Adult ependyma-specific deletion of Ccn1 transiently enhanced NSC proliferation and reduced neuronal differentiation in mice, increasing the numbers of NSCs and NSC units. Although proliferation of NSCs and neurogenesis seen in Ccn1 knockout mice eventually returned to normal, the expanded NSC pool was maintained in the V-SVZ until old age. Inhibition of EGFR signaling prevented expansion of the NSC population observed in CCN1 deficient mice. Thus, ependyma-derived CCN1 restricts NSC expansion in the adult brain to maintain the proper niche capacity of the V-SVZ.
研究领域:
神经科学
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干细胞生物学
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分子生物学
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PubMed
高影响因子
Laser & Photonics Reviews
·
2024
·
IF 9.8
Min Fan,Jingbo Chen,Xiaomeng Zheng,Luyun Xu,Jianqin Ye,Xueliang Lin,Kien Voon Kong,Duo Lin,Yudong Lu,Shangyuan Feng
The emergence of “precision medicine” marks a notable shift in cancer treatment, moving from a tumor type–oriented approach to a more targeted, gene-oriented approach. Detecting low-abundance mutant genes in blood is challenging but crucial for personalized treatment plans. Herein, a novel platform combining catalytic hairpin self-assembly (CHA)-mediated self-calibrating surface-enhanced Raman spectroscopy (SERS) with a high-throughput Raman system (CCSPS) was designed. This platform enables ultrasensitive and rapid genotype analysis of gene mutations. The development of CCSPS specifically targets EGFR mutations, which serve as crucial therapeutic targets for precision therapy in lung cancer. This system shows excellent sensitivity and selectivity, capable of detecting multiple EGFR mutations ( Del-19 , L858R , and T790M ) with a detection limit as low as attomolar levels. Additionally, precise genotyping analysis was successfully conducted on 42 clinical samples using the CCSPS, yielding results consistent with those obtained through next-generation sequencing. These results underscore the efficacy of the CCSPS in noninvasively identifying circulating tumor DNA (ctDNA) mutations, facilitating immediate therapeutic decision making at the bedside. In summary, the CCSPS is a fast, accurate, versatile, and compact testing system capable of precisely screening individuals who stand to benefit from targeted therapy, thus promoting personalized and precise healthcare.
研究领域:
医学
·
分子生物学
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DOI
高影响因子
Oxidative Medicine and Cellular Longevity
·
2022
·
IF 7.31
Yuan Liang,Jingqi Zhao,Haoyang Zou,Jie Zhang,Tiehua Zhang
As the main active ingredients of Panax ginseng, ginsenosides possess numerous bioactivities. Epidermal growth factor receptor (EGFR) was widely used as a valid target in anticancer therapy. Herein, the EGFR targeting activities of 20(S)-ginsenoside Rh2 (20(S)-Rh2) and the relationship of their structure-activity were investigated. Homogeneous time-resolved fluorescence assay showed that 20(S)-Rh2 significantly inhibited the activity against EGFR kinase. 20(S)-Rh2 was confirmed to effectively inhibited cell proliferation in a dose-dependent manner by MTT assay. Furthermore, quantitative real-time PCR and western blotting analysis revealed that 20(S)-Rh2 inhibited A549 cells growth via the EGFR-MAPK pathway. Meanwhile, 20(S)-Rh2 could promote cell apoptosis, block cell cycle, and reduce cell migration of A549 cells, respectively. In silico, the result suggested that both hydrophobic interactions and hydrogen-bonding interactions could contribute to stabilize their binding. Molecular dynamics simulation showed that the side chain sugar moiety of 20(S)-Rh2 was too flexible to be fixed at the active site of EGFR. Collectively, these findings suggested that 20(S)-Rh2 might serve as a potential EGFR tyrosine kinase inhibitor.
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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生物化学
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PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2026
·
IF 7.3
Junhui Ma,Lei Fang,Yu Wu,Hui Jiao,Guangya Xiang,Xiang Ma
Proteolysis-targeting chimeras (PROTACs) are attractive targeted protein degradation modalities, while their clinical advancement is limited by high molecular weight, suboptimal bioavailability, low cellular permeability, and unsatisfactory in vivo efficacy. Herein, we developed a self-assembled nanoparticle system (PRO NPs) constructed from amphiphilic PROTACs. Owing to their intrinsic amphiphilicity, PRO NPs can spontaneously assemble into stable nanoparticles without external excipients, simplifying fabrication and alleviating carrier-associated toxicity. Compared with the free EGFR-targeting PROTAC, PRO NPs exhibited enhanced aqueous solubility and efficient EGFR degradation in HCC827 cells. In vivo, PRO NPs functionalized with hyaluronic acid (HA) through electrostatic adsorption could actively accumulate at tumor sites via CD44-mediated targeting, exerting potent antitumor efficacy (TGI = 76.8%) with reduced systemic toxicity. Collectively, these findings provide novel insights into nano-PROTAC design and a promising strategy for the development of targeted protein degradation therapies.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2026
·
IF 3.6
Yilin Wang,Shenglai Zhou,Xiaopeng Yu,Junfeng Cui,Tengfei Wu
Emerging evidence suggests that triggering ferroptosis could be a promising approach for combating breast cancer. Here, we investigated the role of aurantio-obtusin (AO), a key bioactive compound sourced from Cassiae semen, in the treatment of breast cancer. Cell viability and death were determined via a CCK-8 assay and propidium iodide (PI) staining. Ferroptosis was determined by the levels of Fe2+, lipid ROS, and GSH. Autophagy was assessed by immunofluorescence staining. An MDA-MB-231 cell transplantation tumor model was established in vivo. AO inhibited breast cancer cell growth in a concentration-dependent manner while promoting cell death. Ferroptotic changes, including blockage of the GSH–GPX4 antioxidation system, massive iron release, and lipid ROS accumulation, were evident in AO-treated breast cancer cells. Antioxidant N -acetylcysteine (NAC) treatment markedly restored GSH content and suppressed lipid ROS overproduction to relieve AO-triggered ferroptosis. The introduction of the iron scavenger deferoxamine or the ferroptosis inhibitor ferrostatin-1 weakened AO-induced ferroptosis in breast cancer cells. Moreover, AO treatment promoted autophagosome formation in breast cancer cells via the mTOR-ULK1 pathway. AO-induced autophagy and ferroptosis were both reversed by Atg7 knockdown or mTOR activator MHY1485 treatment. Network pharmacology and molecular docking investigations suggested that EGFR was a potential target of AO in breast cancer and that its protein expression was suppressed by AO. Selective EGFR inhibitor gefitinib exacerbated AO-mediated ferroptosis and autophagy, while genetic overexpression of EGFR completely reversed these AO-mediated phenotypes. In vivo assays confirmed the antitumor effects of AO. Our study revealed that AO facilitated autophagy-dependent ferroptosis in breast cancer cells through the downregulation of EGFR. This work provides a new perspective on the antitumor activity of AO, which is valuable for further investigations of the practical application of AO in breast cancer.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Jingge Sun,Hong Jiang,Qimeng Tian,Yihang Sui,Ling Chen,Yongxiang Wang,Ninghua Tan
Ethnopharmacological relevance Suhuang antitussive capsule (SH) is one of commercially available traditional Chinese medicines (TCMs) used clinically for cough variant asthma (CVA). Over the past decade, our laboratory has systematically investigated the pharmacological properties of SH and established its potent antitussive, anti-inflammatory, expectorant, and antiasthmatic activities. In preliminary screening, rosmarinic acid (RA) detected in SH, showed anti-CVA activity in vitro . Aim of the study This study aimed to investigate the efficacy and mechanism of RA, as an active component of SH, for alleviating CVA. Materials and methods Ovalbumin/aluminum hydroxide (OVA/Al(OH) 3 ) sensitization and challenge created a CVA rat model. Complementary in vitro models were generated by lipopolysaccharide (LPS) stimulation of BEAS-2B and RAW264.7 cells. Therapeutic efficacy was evaluated by cough assay, histopathology, and immune cell counts. Mechanisms were examined by western blotting, immunofluorescence, and immunohistochemistry. Network pharmacology identified EGFR as a key target. Molecular docking, CETSA, and DARTS assays were performed to validate direct RA-EGFR engagement, and agonist rescue experiments tested EGFR-dependent efficacy. Results RA markedly alleviated key CVA-associated phenotypes in vivo , supporting RA as an antitussive component of SH. Consistently, RA attenuated LPS-driven inflammatory activation in BEAS-2B and RAW264.7 cells in vitro . RA downregulated EGFR and suppressed downstream EGFR/ERK and AKT/NF-κB signaling, accompanied by reduced inflammatory responses and improved pathological changes for CVA; these effects were reversed by EGFR agonist stimulation. Conclusion This study demonstrates that RA exerts its therapeutic effect against CVA by inhibiting EGFR, thereby establishing it as a key antitussive component of SH.
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MEDICINAL CHEMISTRY RESEARCH
·
2012
·Vol. 22
·期 2
·986-994
·
IF 1.271
Zhang Mao,Lu Xiang,Zhang Hong-Jia,Li Na,Xiao Yu,Zhu Hai-Liang,Ye Yong-Hao
A series of derivatives of cinnamic amide (compounds 2a – 2v ) were synthesized and evaluated for antiproliferative activities against the human breast cancer cell line MCF-7- and EGFR-inhibitory activities. The structures of compounds 2b and 2i were determined by single-crystal X-ray diffraction analysis. Compounds 2f and 2j showed moderate EGFR inhibitory activity with IC 50 values of 5.16 and 7.37 μM, respectively. Docking simulation of compound 2f was carried out to illustrate the binding mode of the molecule into the EGFR active site. Structure–activity relationship analysis found that the N -phenyl rings are required for enhancing the activities.
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ACS Omega
·
2026
·
IF 5.2
Leina Gao,Dixin Cui,Xu Gao,Xiaoling Luan,Huali Gao
Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the head and neck. Current treatment strategies, including surgery, radiotherapy, and chemotherapy, are limited by moderate efficacy and severe side effects, highlighting the need for novel therapeutic approaches. Wogonin (Wo), a natural flavonoid, has shown antiproliferative, pro-apoptotic, and antimetastatic activities in various cancer models; however, its effect on OSCC has not been investigated. In this study, Wo-loaded poly(lactic-co-glycolic acid) nanoparticles (PW NPs) were prepared to enhance water solubility and achieve sustained drug release. In vitro assays, including CCK-8, flow cytometry, live/dead staining, and wound healing assays, revealed that PW NPs significantly inhibited OSCC cell proliferation, induced apoptosis, and reduced cell migration. Network pharmacology analysis and qRT-PCR further suggested that Wo exerts its therapeutic effects through the EGFR signaling pathway. Hemolysis testing and histological examination of major organs confirmed the favorable biocompatibility of the nanoparticles. This study provides the first systematic evidence of the therapeutic potential of Wo in OSCC and lays a foundation for its further preclinical development.
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BIOMEDICINE & PHARMACOTHERAPY
·
2020
·
IF 4.545
Yuping Liu,Haiyan Xing,Xiangliang Jiang,Yan Chen,Mengmeng Huang,Suyun Yu
Skin toxicities induced by epidermal growth factor receptor inhibitors such as Erlotinib plagues clinical challenges. Chinese formulas have a unique advantage in reducing side effects. Here, we aim to investigate the skin protecting function of XiaoZhenFang (XZF), a clinical adjuvant prescription made up of Lonicerae Japonicae Flos, Lithospermum Erythrorhizon, Smilacis Glabrae Rhizoma, Forsythiae Fructus, Spirodelae Herba, Cortex Moutan and Prunellae Spica. Our data showed that XZF aqueous extract effectively reduced skin toxicities induced by Erlotinib in vivo using established mice model. Next, we used a systems pharmacology approach to investigate the pharmacological mechanism of XZF with the goal of understanding its effects at the system, organ, and molecular levels. 44 candidate compounds and 103 potential targets were identified by network pharmacology. Inflammation, cell stress and the EGFR-related signal pathways, which may participate in the skin protection afforded by XZF, were analyzed by gene enrichment. Importantly, our in vivo experimental results largely validated XZF’s mechanism of action, as predicted by the system pharmacology analysis. Our study uncovered the effect and mechanism of XZF in attenuating skin toxicities induced by EGFRI, providing a basis for the development of in-hospital preparations and new drugs for the prevention of skin toxicities.
研究领域:
药理学
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肿瘤学
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中医药
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分子生物学
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系统生物学
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2017
·
IF 2.981
Guan Huang,Yanli Tong,Qidi He,Jie Wang,Zuanguang Chen
Ethnopharmacological relevance Aucklandia lappa DC. is a widely used medicinal plant in China, India and Pakistan for a long time. Previously, a number of different pharmacological experiments in vitro and in vivo have convincingly demonstrated the abilities of it to exhibit anticancer activities. Reynoutria japonica Houtt. has also been widely used as traditional Chinese medicinal plant. Previous studies have demonstrated that it is bioactive to exhibit anticancer activities. Aim of the study This study aims to investigate whether the extracts of Aucklandia lappa DC. and Reynoutria japonica Houtt. are capable of treating drug-resistant non-small cell lung cancer (NSCLC), providing support for novel usage beyond traditional uses. Materials and methods Extracts combined with gefitinib have been tested taking the vulval development of transgenic C. elegans ( jgIs25 ) as an effective and simple in vivo model system, evaluating their efficacy against acquired NSCLC. Synchronous larval 1 (L1) larvae were treated with extracts plus gefitinib and cultured to obtain mainly L4 larvae. The multivulva (Muv) phenotype was recorded at the adult stage. Results Our data showed that Aucklandia lappa DC. extract could significantly enhance the efficacy of gefitinib, suppressing the Muv phenotype of jgIs25. Meanwhile, it could also down-regulate the mRNA and protein expression of EGFR in jgIs25. Collectively, our results verified that the capability of Aucklandia lappa DC. to inhibit Muv phenotype may be based on the EGFR signaling pathway inhibition. Conclusion We demonstrated that the co-administration of Aucklandia lappa DC. with gefitinib may provide an effective strategy for the therapy of EGFR inhibitor resistant NSCLCs.
研究领域:
民族药理学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2026
·Vol. 19
·期 5
·731
·
IF 5.7
Huiqing Que,Wei Li,Ziting Li,Lihong Ma,Junyong Han,Shenmin Liu,Xiaomei Xu,Liping Qian,Wenjin Lin,Hongxu Liu
Background/Objectives:Triptolide (TP), a potent natural diterpenoid, exhibits anti-glioma activity, but faces significant clinical translation challenges, including poor water solubility, systemic toxicity such as hepatotoxicity, and inadequate tumor targeting. This study aimed to develop a novel epidermal growth factor receptor (EGFR)-targeted liposomal formula-tion, designated as TP-CTX-Lip (where CTX denotes cetuximab), to enhance the deliv-ery efficiency and therapeutic window of TP.Methods:The formulation was optimized using a uniform design approach (four factors, six levels) and prepared via thin-film hydra-tion–ultrasonication. The encapsulation of TP was supported by Fourier transform in-frared spectroscopy (FTIR) and thermal analysis (DSC/TGA), which revealed molecu-lar interactions (e.g., hydrogen bonding) with lipid components and a marked en-hancement in thermal stability, consistent with successful incorporation into the lipo-somal bilayer. The physicochemical properties, including the size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and drug loading, were characterized. In vitro release kinetics were evaluated in phosphate buffer (pH 7.4), and cytotoxicity was assessed in high-EGFR (U87-MG) and low-EGFR (SW1088) glioma cells. In vivo efficacy and developmental toxicity were investigated using zebrafish models. The op-timized TP-CTX-Lip demonstrated favorable characteristics: size = 131.3 ± 4.5 nm, PDI = 0.24 ± 0.006, zeta potential = −23.37 ± 0.27 mV, encapsulation efficiency = 85.83% ± 1.81%, and drug loading = 13%. In vitro release followed first-order kinetics dominated by Higuchi diffusion (79.0% ± 4% at 24 h). After 48 h of treatment, TP-CTX-Lip exhib-ited significantly enhanced cytotoxicity in U87-MG cells (IC50 = 10.4 ± 0.2 nM), com-pared with IC50 values of 42.8 nM in SW1088 cells and 45.3 nM for non-targeted lipo-somes. In the 3T3-L1 non-cancerous cell line, the 48 h IC50 value of TP-CTX-Lip (8.433 ± 0.954µM) was higher than that of the TP solution (2.173 ± 0.181µM) but lower than that of TP-Lip (25.78 ± 2.691µM). Specifically, in 3T3-L1 cells, the 48 h IC50 of TP-CTX-Lip (8.43 µM) was approximately 4-fold higher than that of free TP (2.17 µM), confirming its substantially reduced cytotoxicity against non-cancerous cells.Results:In comparison to TP-Lip and free FITC solution, the uptake rate of TP-CTX-Lip in U87-MG cells exhibited a significantly higher level. Specifically, the uptake rate for the TP-CTX-Lip group (57.46 ± 5.44%) was statistically significantly higher than that of TP-Lip (13.7 ± 2.33%) and the free FITC solution group (20.97 ± 1.60%) (p< 0.01). In zebrafish, TP-CTX-Lip reduced developmental toxicity, with LC50 increased 1.26 times to 5.733 μg/mL, and suppressed orthotopic U87-MG xenograft growth (p< 0.001), in-dicating an improved therapeutic window as reflected by the LC50/IC50 ratio.Conclusions:the EGFR-targeted TP-CTX-Lip significantly enhances the tumor selectivity and safety of TP, providing a promising strategy for targeted glioma therapy.
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MOLECULAR CARCINOGENESIS
·
2018
·Vol. 58
·期 4
·565-576
·
IF 3.851
Hailun Zheng,Lehe Yang,Yanting Kang,Min Chen,Shichong Lin,Youqun Xiang,Caleb Li,Xuanxuan Dai,Xiaoying Huang,Guang Liang,Chengguang Zhao
Several studies have implicated the feedback activation of signal transducer and activator of transcription 3 (STAT3) as a new cancer drug-resistance mechanism and linked it to the failure of epidermal growth factor receptor (EGFR)-targeted therapies. In this study, we discovered that Alantolactone, a natural sesquiterpene lactone, potently inhibited human pancreatic cancer cells and suppressed constitutively activated STAT3. In contrast, Alantolactone had little effect on the EGFR pathway. Moreover, combination of Alantolactone and an EGFR inhibitor, Erlotinib or Afatinib, demonstrated a remarkable synergistic anti-cancer effect against pancreatic cancer cells both in vitro and in vivo. Our results suggested that Alantolactone could sensitize human pancreatic cancer cells to EGFR inhibitors possibly through down-regulating the STAT3 signaling. Alantolactone, when combined with other EGFR targeted agents, could be further developed as a potential therapy for pancreatic cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）