SENSORS AND ACTUATORS B-CHEMICAL
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2024
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IF 8
Yuanyuan Sun,Lingling Zhao,Chunxia Wu,Yanru Chen,Guang-Li Wang
Photoelectrochemical (PEC) bioanalysis has recently become a perspective pathway for biomolecular sensing, presenting new insights for disease diagnosis and treatment. Herein, we present a new cathodic PEC platform for detecting Src kinase in a label-free, non-immobilized, and high-throughput mode. Specifically, treatment of the tyrosine-containing peptide by tyrosine kinase produced an ortho-diphenol structure of tyrosine that can in situ introduce oxygen vacancies (Ov) on the surface of NiTiO 3 material, which led to the augmentation of the photoelectric signal. While the presence of the target Src kinase phosphorylated tyrosine in substrate peptide and blocked the surface Ov formation onto NiTiO 3 . Such a phenomenon was correlated with the Src kinase detection in terms of good sensitivity and selectivity, achieving the linear detection range of 0.001–2.0 μg/mL and the detection limit of 3.0×10 −4 μg/mL (S/N=3). For Src kinase detection, this is a superior strategy to some classical methods in terms of easy operation, rapid response, and cost effectiveness. This study features the first exploration of cathodic photoelectrochemistry for Src kinase detection and is expected to expand its application in probing more disease related targets with unknown possibilities.
研究领域:
生物传感
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疾病诊断
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光电化学
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DOI
高影响因子
Experimental and Therapeutic Medicine
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2021
·Vol. 21
·期 6
·1-11
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IF 2.447
Xiaoming Lin,Guangfei Wang,Ping Liu,Lei Han,Tong Wang,Kaili Chen,Yonglin Gao
The aim of the present study was to investigate the effects of gallic acid (GA) on the proliferation and apoptosis of colon cancer cells and to further clarify the mechanism of GA function associated with SRC and EGFR phosphorylation. HCT116 and HT29 cells were treated with different concentrations of GA for 24 h. Cell proliferation and apoptosis were analyzed using plate clone formation and flow cytometry assays, respectively. In addition, the expression of apoptosis‑related proteins was examined by western blotting. Furthermore, the level of STAT3, AKT, SRC and EGFR phosphorylation was analyzed by western blotting and immunofluorescence. Subsequently, the SRC inhibitor PP2 and the EGFR inhibitor gefitinib were used to analyze the GA‑associated mechanisms. In addition, a xenograft tumor model was established to confirm the effects of GA in vivo. The results indicated that GA inhibited cell proliferation and promoted cell apoptosis by upregulating the ratio of cleaved caspase‑3/pro‑caspase‑3 and cleaved caspase‑9/pro‑caspase‑9. Concurrently, GA decreased the level of phosphorylated (p)‑SRC, p‑EGFR, p‑AKT and p‑STAT3. Following treatment with PP2 and gefitinib in both cancer cell lines and animal model, GA was demonstrated to inhibit EGFR and SRC phosphorylation to downregulate STAT3 and AKT phosphorylation. In vivo, GA prevented tumor growth, promoted tumor apoptosis and decreased the level of p‑SRC, p‑EGFR, p‑STAT3 and p‑AKT. In conclusion, GA was indicated to suppress colon cancer proliferation by inhibiting SRC and EGFR 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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DOI
PubMed
高影响因子
LIFE SCIENCES
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2025
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IF 5.1
Qing Li,Mei Zhou,Ying Yang,Yangming Jiang,Chao Chen,Enming Hu,Jialin Chen,Daoping Wang
Overexpression of EphB3 has been documented across various cancers and essential for cell proliferation, survive and metastasis, making it a valuable therapeutic target. In this study, a series of novel penta-1,4-dien-3-one and quinoxaline conjugates were designed and synthesized using pharmacophore fusion strategies to explore potential EphB3 inhibitors. CCK-8 experiments revealed significant anti-cancer activity of most newly synthesized compounds against hepatocellular carcinoma (HCC). Among them, compound W8 displaying the highest inhibitory activity against MHCC97H (IC 50 = 1.87 μM), which arrests MHCC97H cells in the G0/G1 phase and induces apoptosis. Furthermore, compound W8 suppresses tumor growth in an MHCC97H xenograft model in vivo by suppressing phosphorylation level of EphB3 and down-regulating the SRC-AKT signaling pathway, leading to a dose-dependent reduction in tumor volumes and weights, with a 40 mg/kg dose achieving decreases of 68.4 % and 65.3 %, respectively. Given its ability to modulate EphB3 signaling, W8 represents a promising lead compound for further drug development, particularly for cancers characterized by EphB3 overexpression, and may offer new opportunities for targeted therapy in precision oncology.
研究领域:
肿瘤学
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药物化学
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分子生物学
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DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2025
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IF 8.2
Yan Zhang,Yuanyuan Ren,Zhen Wang,Xi Zhang,Xiaofang Li,Yi Yu,Lu Qian,Yuyan Xiong
A high-fat diet and obesity significantly increase the risk of gastric cancer (GC), with persistent obesity contributing to a notable rise in GC incidence. However, the underlying molecular mechanisms remain largely unclear. In this study, we identified exosomal SLC1A5 (Exo-SLC1A5) as a novel senescence-associated secretory phenotype (SASP) factor that promotes GC malignancy. Exosomal SLC1A5 drives GC progression by suppressing ferroptosis in a GPX4-dependent manner. Mechanistically, in the context of obesity, senescent endothelial cells release exosomal SLC1A5, which engages EGFR on GC cells, triggering SRC phosphorylation at Tyr416 and subsequent YAP1 activation at Tyr357. This leads to YAP1 interaction with MYO1B to enhance the nuclear translocation of YAP1, and subsequent upregulation of GPX4, resulting in ferroptosis suppression and accelerated GC progression. In vivo, depletion of exosomal SLC1A5 from PA-induced senescent ECs attenuated GC tumor growth and metastasis in a xenograft mouse model. These findings reveal a novel mechanism by which exosomal SLC1A5 promotes GC progression through the EGFR/SRC/YAP1/GPX4 signaling axis. Targeting the Exo-SLC1A5/EGFR/SRC/YAP1/GPX4 axis may provide a therapeutic strategy for GC.
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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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2025
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IF 4.8
Yancen Li,Chengyu Wan,Fan Li,Guang Xin,Tao Wang,Qilong Zhou,Tingyu Wen,Shiyi Li,Xiaoting Chen,Wen Huang
Background: Isatidis Folium, a botanical drug widely used in traditional medicine, is known for its anti-inflammatory properties, including heat-clearing, detoxifying, and blood-cooling effects. Although its potential in sepsis treatment has been suggested, the bioactive metabolites and underlying mechanisms remain poorly understood.Methods: Network pharmacology and molecular docking were employed to identify the therapeutic effects and mechanisms of Indirubin, the major bioactive metabolite of Isatidis Folium, in sepsis treatment. In vivo, a cecal ligation and puncture (CLP)-induced mouse sepsis model was used to evaluate the protective effects of Indirubin through histopathological analysis, ELISA, and biochemical assays. In vitro, RAW264.7 cells were stimulated with LPS and treated with varying concentrations of Indirubin. The anti-inflammatory effects of Indirubin were assessed using ELISA, apoptosis assays, and Western blotting.Results: Network pharmacology analysis identified Indirubin as the major bioactive metabolite of Isatidis Folium and EGFR and SRC as its key molecular targets. Experimental validation demonstrated that Indirubin significantly improved survival rates, alleviated tissue injury, and suppressed inflammatory responses in sepsis models. Mechanistically, Indirubin inhibited LPS-induced activation of the EGFR/SRC/PI3K and NF-κB/MAPK pathways in macrophages, significantly reducing cell death and inflammation in RAW264.7 cells.Conclusion: Indirubin, the primary bioactive metabolite of Isatidis Folium, exerts protective effects against sepsis by targeting the EGFR/SRC/PI3K and NF-κB/MAPK signaling pathways in macrophages. These findings provide a mechanistic basis for the development of Indirubin as a multi-target therapeutic agent for sepsis treatment.
研究领域:
药理学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
Molecular Cancer
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2022
·Vol. 21
·期 1
·1-17
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IF 41.444
Pan Zhenzhen,Wang Kai,Wang Xiniao,Jia Zhirong,Yang Yuqi,Duan Yalei,Huang Lianzhan,Wu Zhuo-Xun,Zhang Jian-ye,Ding Xuansheng
Background The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) brings remarkable benefits for the survival of patients with advanced NSCLC harboring EGFR mutations. Unfortunately, acquired resistance seems to be inevitable and limits the application of EGFR-TKIs in clinical practice. This study reported a common molecular mechanism sustaining resistance and potential treatment options to overcome EGFR-TKIs resistance.Methods EGFR-TKIs resistant NSCLC cells were established and confirmed by MTT assay. Cholesterol content was detected and the promotional function of cholesterol on NSCLC growth was determined in vivo. Then, we identified ERRα expression as the downstream factor of cholesterol-mediated drug resistance. To dissect the regulatory mechanism, we conducted experiments, including immunofluorescence, co-immunoprecipitation, luciferase reporter assay and chromatin immunoprecipitation assay.Results Long-term exposure to EGFR-TKIs generate drug resistance with the characteristic of cholesterol accumulation in lipid rafts, which promotes EGFR and Src to interact and lead EGFR/Src/Erk signaling reactivation-mediated SP1 nuclear translocation and ERRα re-expression. Further investigation identifies ERRα as a target gene of SP1. Functionally, re-expression of ERRα sustains cell proliferation by regulating ROS detoxification process. Lovastatin, a drug used to decrease cholesterol level, and XCT790, an inverse agonist of ERRα, overcome gefitinib and osimertinib resistance both in vitro and in vivo.Conclusion sOur study indicates that cholesterol/EGFR/Src/Erk/SP1 axis-induced ERRα re-expression promotes survival of gefitinib and osimertinib-resistant cancer cells. Besides, we demonstrate the potential of lowing cholesterol and downregulation of ERRα as effective adjuvant treatment of NSCLC.
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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DOI
PubMed
高影响因子
Chinese Journal of Integrative Medicine
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2024
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IF 2.2
Liu Xiao-rong,Li Shuo-fu,Mei Wen-ya,Liu Xiang-dan,Zhou Ri-bao
Objective To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis (RA). Methods Tumor necrosis factor (TNF)- α -induced fibroblast-like synoviocytes (FLS) was exposed to additional isorhamnetin (10, 20 and 40 µ mol/L). Overexpression vectors for matrix metalloproteinase-2 (MMP2) or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function. RA-FLS viability, migration, and invasion were evaluated. Moreover, a collagen-induced arthritis (CIA) rat model was established. Rats were randomly divided to sham, CIA, low-, medium-, and high-dosage groups using a random number table ( n =5 in each group) and administed with normal saline or additional isorhamnetin [2, 10, and 20 mg/(kg·day)] for 4 weeks, respectively. Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats. The levels of MMP2, MMP9, TNF-α, interleukin-6 (IL-6), and IL-1 β, as well as the phosphorylation levels of SRC, extracellular regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding (CREB), were detected in RA-FLS and synovial tissue. Molecular docking was also used to analyze the binding of isorhamnetin to SRC. Results In in vitro studies, isorhamnetin inhibited RA-FLS viability, migration and invasion ( P <0.05). Isorhamnetin downregulated the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 β in RA-FLS ( P <0.05). The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion, as well as the levels of TNF-α, IL-6, and IL-1 β ( P <0.05). Furthermore, isorhamnetin bound to SRC and reduced the phosphorylation of SRC, ERK, and CREB ( P <0.05). SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability, migration and invasion, as well as the negative regulation of MMP2 and MMP9 ( P <0.05). In in vivo studies, isorhamnetin decreased arthritis index scores ( P <0.05) and alleviated synovial inflammation. Isorhamnetin reduced the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 β, as well as the phosphorylation of SRC, ERK, and CREB in synovial tissue ( P <0.05). Notably, the inhibitory effect of isorhamnetin was more pronounced at higher concentrations ( P <0.05). Conclusion Isorhamnetin exhibited anti-RA effects through modulating SRC/ERK/CREB and MMP2/MMP9 signaling pathways, suggesting that isorhamnetin may be a potential therapeutic agent for RA.
研究领域:
药理学
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免疫学
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风湿病学
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分子生物学
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DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
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2024
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IF 14.7
Xiong Chen,Jinfu Qian,Shiqi Liang,Jianchang Qian,Wu Luo,Yujuan Shi,Hong Zhu,Xiang Hu,Gaojun Wu,Xiaokun Li,Guang Liang
Protein tyrosine kinases (RTKs) modulate a wide range of pathophysiological events in several non-malignant disorders, including diabetic complications. To find new targets driving the development of diabetic cardiomyopathy (DCM), we profiled an RTKs phosphorylation array in diabetic mouse hearts and identified increased phosphorylated fibroblast growth factor receptor 1 (p-FGFR1) levels in cardiomyocytes, indicating that FGFR1 may contribute to the pathogenesis of DCM. Using primary cardiomyocytes and H9C2 cell lines, we discovered that high-concentration glucose (HG) transactivates FGFR1 kinase domain through toll-like receptor 4 (TLR4) and c-Src, independent of FGF ligands. Knocking down the levels of either TLR4 or c-Src prevents HG-activated FGFR1 in cardiomyocytes. RNA-sequencing analysis indicates that the elevated FGFR1 activity induces pro-inflammatory responses via MAPKs–NF κ B signaling pathway in HG-challenged cardiomyocytes, which further results in fibrosis and hypertrophy. We then generated cardiomyocyte-specific FGFR1 knockout mice and showed that a lack of FGFR1 in cardiomyocytes prevents diabetes-induced cardiac inflammation and preserves cardiac function in mice. Pharmacological inhibition of FGFR1 by a selective inhibitor, AZD4547, also prevents cardiac inflammation, fibrosis, and dysfunction in both type 1 and type 2 diabetic mice. These studies have identified FGFR1 as a new player in driving DCM and support further testing of FGFR1 inhibitors for possible cardioprotective benefits.
研究领域:
心脏病学
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糖尿病
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分子生物学
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药理学
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DOI
PubMed
高影响因子
REPRODUCTIVE TOXICOLOGY
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2025
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IF 2.8
Huan Li,Hongyan Wang,Xiaolei Xu,Li Qu,Xiuling Sun,Jing Zhang
This study aimed to investigate the protective mechanism of Ginsenoside Rg3 (Rg3) against Di-n-butyl phthalate (DBP) induced spermatogenic damage, focusing on the Src/PI3K/Akt pathway. In vivo experiments demonstrated that Rg3 restored DBP-induced dysregulation of gap junction (GJ) protein connexin 43 (Cx43), improved testicular structure, enhanced sperm parameters (count and motility), and upregulated phosphorylation of Src, PI3K, and Akt (p-Src, p-PI3K, p-Akt) in mice. In vitro studies, using the metabolite of DBP, monobutyl phthalate (MBP), and pathway inhibitors (PP2 for Src and LY294002 for PI3K), further confirmed these effects. Rg3 increased antioxidant enzyme activity, reduced oxidative stress marker MDA, and enhanced the expression of p-Src, p-PI3K, p-Akt, and Cx43 in MBP-treated TM4 Sertoli cells. Inhibitor experiments confirmed that the Src/PI3K pathway mediates Rg3’s protective action. These findings suggest that Rg3 alleviates DBP/MBP-induced male reproductive dysfunction by enhancing antioxidant capacity and reactivating the Src/PI3K/Akt signaling pathway, which helps restore blood-testis barrier (BTB) integrity through Cx43 stabilization. Thus, Rg3 may serve as a potential therapeutic agent for environmental toxicant-related male infertility.
研究领域:
药理学
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毒理学
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生殖生物学
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细胞信号传导
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环境卫生
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DOI
PubMed
高影响因子
International Journal of Biological Sciences
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2021
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IF 6.582
Deng-Pan Wu,Yan Zhou,Li-Xiang Hou,Xiao-Xiao Zhu,Wen Yi,Si-Man Yang,Tian-Yu Lin,Jin-Lan Huang,Bei Zhang,Xiao-Xing Yin
Tamoxifen (TAM) resistance has indicated a significant challenge during endocrine therapy for hormone-sensitive breast cancer. Thus, it is significant to elucidate the molecular events endowing TAM resistance to endocrine therapy. In this study, we found that epithelial-mesenchymal transition (EMT) was an important event to confer TAM resistance, and attenuating EMT by elevating connexin (Cx) 43 expression could reverse TAM resistance. Specifically, Cx43 overexpression improved TAM sensitivity, while Cx43 depletion facilitated TAM insensitivity by modulating EMT in T47D TAM-resistant and -sensitive cells, and transplanted xenografts. Importantly, we found a novel reciprocal regulation between Cx43 and c-Src/PI3K/Akt pathway contributing to EMT and TAM resistance in breast cancer. Moreover, we identified that Cx43 deficiency was significantly correlated with poor relapse-free survival in patients undergoing TAM treatment. Therefore, Cx43 represents a prognostic marker and an attractive target for breast cancer treatments. Therapeutic strategies designed to increase or maintain Cx43 function may be beneficial to overcome TAM resistance.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
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2025
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IF 4.9
Zhiru Yang,Haolin Guo,Pengfei Zhang,Kairui Liu,Junli Ba,Xue Bai,Shiti Shama,Bo Zhang,Xiaoning Gao,Jun Kang
Ethanol (EtOH) is a common trigger for gastric mucosal diseases, and mitigating oxidative stress is essential for attenuating gastric mucosal damage. Capsaicin (CAP) has been identified as a potential agent to counteract oxidative damage in the gastric mucosa; however, its precise mechanism remains unclear. This study demonstrates that CAP alleviates EtOH-induced gastric mucosal injuries through two primary pathways: by suppressing the chemokine receptor 4 (CCR4)/Src/p47phox axis, thereby reducing oxidative stress, and by inhibiting the phosphorylation and nuclear translocation of nuclear factor- κ B p65 (NF- κ B) p65, resulting in diminished inflammatory responses. These findings elucidate the mechanistic pathways of CAP and provide a theoretical foundation for its potential therapeutic application in the treatment of gastric mucosal injuries.
研究领域:
药理学
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胃肠病学
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DOI
PubMed
高影响因子
Drug Design Development and Therapy
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2022
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IF 4.319
Jiabin Zhou,Fengqi Zhang,Jun Chen,Shilin Zhang,Haijun Wang
Introduction Chlorogenic acid (CGA) is a type of polyphenolic substance that is widely extracted from many traditional Chinese medicines (eg, Lonicera japonica Thunb, Eucommia ulmoides Oliver) and exhibits a wide range of anti-tumor effects. However, the potential molecular mechanisms of CGA in glioma U373 cells remain unclear.Methods Network pharmacology analysis was used to explore the potential therapeutic targets of CGA in glioma. Human glioma U373 cells were treated with different concentrations of CGA for 24 h. CCK-8 assays were used to detect the inhibitory rate of cell growth. Annexin V-FITC/PI staining and Hoechst 33342 staining were used to detect apoptosis. PI staining was used to investigate cell-cycle progression. Wound healing assays and transwell assays were used to detect the cell migration and invasion, respectively. Western blotting and immunohistochemistry were used to measure protein levels in vitro and in vivo.Results The proliferation of U373 cells was significantly inhibited by CGA in a dose- and time-dependent manner. CGA significantly arrested the cell cycle of U373 cells in the G2/M phase and induced apoptosis. Moreover, CGA significantly suppressed the migration and invasion of U373 cells. Additionally, we found that CGA inhibited the growth of U373 cells in vivo. Furthermore, network pharmacology analysis suggested that the anti-tumor effects of CGA on U373 cells were associated with the down-regulation of the SRC/MAPKs signaling pathway.Discussion The present study indicated that CGA had anti-glioma effects on U373 cells by down-regulating SRC/MAPKs signal pathway.
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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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）