SENSORS AND ACTUATORS B-CHEMICAL
·
2020
·
IF 7.1
Bo-Xin Zheng,Wei Long,Yi-Han Zhang,Xuan-He Huang,Cui-Cui Chen,Dong-Xiao Zhong,Meng-Ting She,Ze-Xin Chen,Dong-Peng Cai,Yu-Jing Lu,Wing-Leung Wong
Red fluorescent G-quadruplex DNA selective organic binding probe is relatively underdeveloped. In the present study, we designed a series of new fluorescent probes that exhibit large Stokes shift (112−131 nm), high quantum yield (up to 0.56), robust against photo-bleaching and high selectivity towards quadruplex structures of c-MYC and telomere DNA with strong binding affinity . The discrimination ability of the probes towards G-quadruplex structures against single-/double-stranded DNA or RNA was investigated by analyzing their structural property with respect to their binding specificity. From the sensing application of the probe targeting pu27, an excellent linear relationship (R 2 = 0.9997) with respect to the pu27- A3 interaction signal was observed. The LOD was found down to 4.0 nM, which is superior to thiazole orange dye. The probe is able to realize real-time fluorescence visualization in aqueous, PAGE staining and live cell imaging. In addition, from the immunofluorescence analysis using the probe and BG4 antibody, the A3 foci and BG4 staining co-localized well in PC3 cells, which suggest that the probe is G-quadruplex selective and is useful for visualizing G-quadruplex DNA structures in live cells. Cytotoxicity assays also demonstrated that the probe has low cytotoxicity against both PC3 cancer cells and 16HBE normal cells.
研究领域:
生物化学
·
分子生物学
·
医学诊断
✓ 已验证
DOI
高影响因子
Translational Research
·
2026
·
IF 6.1
Lu Han,Guo-Yuan Lin,Shao-Jie Chen,Qing-Xiu Zhang,Hua-Yue Wu,Tao Huang,Fan Lu,Hong-Fei Pu,Jing-Lin Wang,Tao Ran,Gao-Liang Zou,Jian-Chao Li,Ya Zhang,Xue-Ke Zhao
Liver fibrosis is marked by hepatic stellate cell (HSC) activation and increased glucose consumption. Focal adhesion kinase (FAK) upregulates c-Myc expression in HSCs, promoting aerobic glycolysis. This study explores how FAK promotes HSC activation and glycolysis via TRIM25. Immunohistochemistry (IHC) and Western blotting assessed the expression of FAK, TRIM25, FBXW7, c-Myc, and glycolysis-related proteins in human liver tissues and mouse models. Protein interactions were identified by co-immunoprecipitation (Co-IP) and LC-MS, and FAK and TRIM25 localization was observed by immunofluorescence. FAK inhibition reduced LX-2 cell activation, migration, and glycolysis. Co-IP and immunofluorescence confirmed FAK-TRIM25 interaction. FAK inhibits FBXW7-mediated c-Myc ubiquitination and enhances glycolysis by binding TRIM25’s RING, B-BOX, and SPRY regions. Inhibition of FAK improved liver fibrosis and glycolysis. FAK promotes HSC glycolysis through TRIM25 interaction, and its inhibition mitigates liver fibrosis, suggesting a potential therapeutic target.
✓ 已验证
DOI
PubMed
高影响因子
Marine Drugs
·
2021
·Vol. 19
·期 2
·79
·
IF 5.118
Hengju Ge,Di Zhang,Muran Shi,Xiaoyuan Lian,Zhizhen Zhang
In 2019, streptoglutarimide H (SGH) was characterized as a new glutarimide from the secondary metabolites produced by a marine-derived actinomyceteStreptomycessp. ZZ741 and shown to have in vitro antiglioma activity. However, the antiproliferative activity and potential mechanism of SGH against lung cancer cells have not yet been characterized. This study demonstrated that SGH significantly inhibited the proliferation of different lung cancer cells. In terms of mechanism of action, SGH downregulated cell cycle- and nucleotide synthesis-related proteins to block cell cycle at G0/G1 phase, reduced the expression levels of glycolytic metabolic enzymes to inhibit glycolysis, and downregulated the important cancer transcription factor c-Myc and the therapeutic target deubiquitinase USP28. Potent anticancer activity and multiple mechanisms indicated SGH to be a novel antitumor compound against lung cancer cells.Keywords:Streptoglutarimide H;lung cancer cells;antiproliferative activity;cell cycle block;glycolysis;USP28;c-Myc
研究领域:
肿瘤学
·
药理学
·
海洋生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Shuting Han,Jiaru Wang,Jiao Xue,Junjie Miao,Xingyu Liu,Shuhui Yin,Qian Wang,Jing Jin
Chemoresistance is a significant factor in the failure of cancer treatment. Although some chemotherapeutic combination regimens are linked to DNA damage repair processes, the therapeutic potential of TCM-derived small molecules that target these mechanisms is still underexplored. Alloimperatorin (Alloi) has demonstrated the ability to inhibit tumor growth; however, the efficacy and molecular mechanisms of its combination with chemotherapeutic agents are not yet fully understood. Here, we demonstrate that Alloi sensitizes multiple tumor cell lines to gemcitabine (GEM) both in vitro and in vivo. Using functional assays, we confirmed a potent synergistic inhibitory effect of the Alloi-GEM combination, which markedly suppressed pancreatic cancer progression in vivo with minimal adverse effects. By integrating transcriptome sequencing with network pharmacology, we identified downregulation of c-MYC and Nijmegen Breakage Syndrome 1 gene (NBS1) as a key mechanistic event, a finding subsequently validated through multiple assays. Mechanistically, the Alloi-GEM regimen induces sustained DNA damage via disruption of the c-MYC-NBS1 axis, thereby impairing the DNA damage response pathway. Collectively, our findings establish that Alloi enhances tumor sensitivity to GEM through modulation of the c-MYC/NBS1 axis and identify this combinatorial strategy as a promising approach for cancer treatment. Alloi enhances the antitumor effect of GEM by suppressing the c-MYC/NBS1 axis. Downregulation of c-MYC reduces NBS1 expression and impairs MRN complex-mediated DNA damage response signaling, including ATM/CHK2 activation and DNA repair. As a result, GEM-induced DNA damage is sustained, ultimately promoting tumor cell death. Download: Download high-res image (238KB) Download: Download full-size image
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2025
·
IF 3.8
Si Mengyao,Han Guo,Liu Tianwen,Wang Xiaoying
Aberrant overexpression of c-Myc protein (c-Myc) serves as a critical biomarker for aggressive lymphomas, yet its trace-level quantification remains challenging due to insufficient sensitivity in conventional assays. Here, we present an electrochemical immunosensor leveraging homogeneous gold–palladium (AuPd) nanohybrids for dual amplification, achieving both simplified fabrication and enhanced analytical performance. A chitosan–graphene oxide–AuPd nanorod composite (CS-GO-AuPd) was engineered as an electrode modifier, offering high conductivity, biocompatibility, and abundant antibody immobilization sites. Prussian blue-doped AuPd nanoparticles (PB-AuPd@Ab 2 ) were simultaneously designed as catalytic signal probes, synergistically amplifying responses through electron mediation and nanozyme activity. This homogeneous material strategy eliminated heterogeneous nanomaterial interfaces, streamlining sensor assembly while ensuring signal reproducibility. The sandwich-type immunocomplex formation triggered a PB-derived differential pulse voltammetry signal proportional to c-Myc concentration, yielding a 0.5 pg mL −1 –1 ng mL −1 linear range, with a detection limit of 0.25 pg mL −1 . Comparative validation against clinical methods confirmed robust accuracy, highlighting the platform’s potential for dynamic monitoring of lymphoma progression and therapy response. This work establishes a paradigm for unifying material homogeneity with dual-amplification mechanisms in biosensing, extensible to diverse low-abundance biomarkers. Graphical
研究领域:
生物传感器
·
纳米材料
·
电化学
·
癌症诊断
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Qianqian Zheng,Gui Mei,Ping Cheng,Yahong Li,Qingfeng Zhang,Mingwei Ye
Given the demonstrated mitigating effect of omega-9 monounsaturated fatty acids (ω-9MUFAs) on lipopolysaccharide (LPS)-induced acute lung injury (ALI), we deeply explored corresponding mechanisms. Sprague-Dawley rats experienced ALI modeling, and received ω-9 MUFAs (3 mg/kg) injection via the tail vein. Post incubation in 100 ng/mL phorbol-12-myristate-13-acetate and 100 ng/mL LPS for 24 h each, THP-1 macrophages were transfected with shHSPH1 and c-MYC overexpression plasmid. Lung injury detection depended on H&E staining. Levels of inflammation-related factors were detected by ELISA. Levels of inflammation-related factors, heat shock protein family H (Hsp110) member 1 (HSPH1), c-MYC, stimulator of interferon response CGAMP interactor 1 (STING) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) were measured by qRT-PCR. Levels of pyroptosis-related factors, HSPH1, c-MYC, STING, NLRP3, and M1 macrophage biomarkers were assayed by Western blot. Proportion of M1 macrophages and pyroptosis were detected by flow cytometry. Localization of HSPH1 and CD68 was measured by immunofluorescence assay. ω-9MUFAs reduced the inflammation, the proportion of M1 and pyroptotic macrophages and levels of HSPH1, c-MYC, STING and NLRP3 in ALI rats. The expression positions of HSPH1 and CD68 were overlapped in ALI rat lung tissue. HSPH1 silencing reversed the changes in inflammation, the proportion of M1 and pyroptotic macrophages and levels of c-MYC, STING and NLRP3 in LPS-induced THP-1 macrophages, and c-MYC overexpression offset these effects of HSPH1 silencing. Collectively, ω-9MUFAs ameliorated LPS-induced ALI by regulating HSPH1/c-MYC expression, down-regulating M1 macrophage polarization and pyroptosis.
研究领域:
免疫学
·
分子生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Oncology
·
2021
·
IF 4.375
Xiaodan Sun,Peiyan Zhao,Hui Li,Yan Liu,Tianming Wang,Ying Cheng
Ginsenoside Rh2 (Rh2) is one of the pharmacologically active components of ginseng with an antitumor effect. However, its effect on non-small-cell lung cancer (NSCLC), especially on aerobic glycolysis, which plays a crucial role in the proliferation and progression of tumor cells, has not been characterized. Here, we demonstrated that Rh2 inhibited the proliferation and metastasis of NSCLC cells by promoting apoptosis and suppressing epithelial-mesenchymal transition, respectively. Notably, Rh2 exerted a glycolysis inhibition effect through regulating GLUT1, PKM2, and LDHA, which are key enzymes of the glycolysis process. Furthermore, the metabolic shift function of Rh2 was dependent on the STAT3/c-Myc axis in NSCLC. This novel regulatory role of Rh2 provides a new perspective for NSCLC treatment and highlights the potentiality of Rh2 to be used as a tumor energy blocker. The combination of Rh2 with an STAT3 or c-Myc inhibitor revealed a promising therapeutic approach for patients with NSCLC.
研究领域:
肿瘤学
·
药理学
·
代谢途径
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Mengyang Wang,Wu Luo,Tianxiang Yu,Shiqi Liang,Chunpeng Zou,Jinfeng Sun,Gao Li,Guang Liang
Background Heart failure is a common event in the course of hypertension. Recent studies have highlighted the key role of the non-hemodynamic activity of angiotensin II (Ang II) in hypertension-related cardiac inflammation and remodeling. A naturally occurring compound, diacerein , exhibits anti-inflammatory activities in various systems. Hypothesis/Purpose In this study, we have examined the potential effects of diacerein on Ang II-induced heart failure. Methods C57BL/6 mice were administered Ang II by micro-osmotic pump infusion for 4 weeks to develop hypertensive heart failure. Mice were treated with diacerein by gavage for final 2 weeks. RNA-sequencing analysis was performed to explore the potential mechanism of diacerein. Results We found that diacerein could inhibit inflammation, myocardial fibrosis , and hypertrophy to prevent heart dysfunction, without the alteration of blood pressure. To explore the potential mechanism of diacerein, RNA-sequencing analysis was performed, indicating that MAPKs/c-Myc pathway is involved in that cardioprotective effects of Diacerein. We further confirmed that diacerein inhibits Ang II-activated MAPKs/c-Myc pathway to reduce inflammatory response in mouse hearts and cultured cardiomyocytes . Deficiency of MAPKs or c-Myc in cardiomyocytes abolished the anti-inflammatory effects of diacerein. Conclusion Our results indicate that diacerein protects hearts in Ang II-induced mice through inhibiting MAPKs/c-Myc-mediated inflammatory responses, rendering diacerein a potential therapeutic candidate agent for hypertensive heart failure.
研究领域:
心脏病学
·
药理学
·
分子生物学
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND FUNCTION
·
2026
·Vol. 44
·期 10
·e70320
·
IF 3.5
Caifang Sun,Meijuan Yue,Yuxiang Chen,Jiaying Zhang,Yunyun Mai,Yuhang Zhang,Bingyu Ye
The transcription factor zinc finger protein 143 (ZNF143) plays a crucial role in regulating diverse biological processes, including cell cycle progression, development, and cellular differentiation. Similarly, c-Myc is well-established as a key regulator of cell proliferation, differentiation, and metabolic homeostasis. While studies have demonstrated ZNF143's involvement in the proliferation of both normal hepatocytes and hepatoma cells, the precise mechanisms underlying ZNF143-mediated regulation of hepatocyte proliferation, as well as its potential functional interplay with c-Myc in this process, remain to be fully elucidated. In this study, we investigated the dynamic expression patterns of ZNF143 and c-Myc during distinct phases of liver regeneration using a 2/3 partial hepatectomy (PHx) mouse model. To elucidate the regulatory roles of these factors in hepatocyte proliferation, we employed the mouse normal hepatocyte line AML12 and the human hepatoma cell line Huh7 as experimental models. Through MTT, CCK-8, EdU, quantitative real-time PCR (qRT-PCR), and Western blot, we examined the individual and combined effects of ZNF143 and c-Myc on hepatocyte proliferation. Our findings reveal that ZNF143 inhibits proliferation and cell cycle progression in AML12 cells but promotes these processes in Huh7 cells. Notably, co-overexpression (OE) of ZNF143 and c-Myc in AML12 cells inhibited proliferation and cell cycle progression, suggesting that ZNF143 exerts a dominant regulatory effect over c-Myc in normal hepatocytes. This study establishes a critical foundation for investigating the role of ZNF143 in hepatocyte proliferation in vivo, with potential implications for liver regeneration and transplantation therapies. Significance Statement The transcription factor ZNF143, which contains seven zinc finger domains, has been extensively studied in various cancers. However, its role and underlying mechanisms in liver regeneration remain largely unexplored. Here, we report the dynamic expression pattern of ZNF143 in a mouse liver regeneration model, suggesting its potential involvement in hepatocyte proliferation. Utilizing two cell lines, AML12 and Huh7, our study revealed that ZNF143 exerts opposing effects on cell proliferation and the cell cycle in normal hepatocytes versus hepatocellular carcinoma cells. Mechanistically, ZNF143 regulates these processes by suppressing c-Myc expression. Future work focused on designing targeted therapies based on the regulatory model of ZNF143 could represent a significant strategy for addressing challenges in both liver regeneration and liver disease.
✓ 已验证
DOI
高影响因子
BIOORGANIC CHEMISTRY
·
2020
·
IF 4.831
Qiong Wu,Yue Song,Ruotong Liu,Rui Wang,Wenjie Mei,Weiming Chen,Huanglan Yang,Xicheng Wang
Phenanthroimidazole derivatives containing phenanthroline and imidazole heterocyclic aromatic rings are effective agents to inhibit tumor cell growth. Herein, halogen element-modified imidazo[4,5 f ][1,10]phenanthroline derivatives 1–6 ( 1 , 4-fluorophenyl; 2 , 4-chlorophenyl; 3 , 4-bromobenyl; 4 , 2,3-dichlorophenyl; 5 , 3,4-dichlorophenyl; and 6 , 2,4-dichlorophenyl) were synthesized, and their antitumor activities were investigated. All of the compounds, especially 4 , exhibited an excellent inhibitory effect against nasopharyngeal carcinoma CNE-1 cells. This effect was better than that of doxorubicin. Compound 4 also markedly blocked the proliferation of the CNE-1 cells in a zebrafish xenograft model. The antitumor mechanisms might be attributed to apoptosis induction, which triggered ROS-mediated DNA damage and generated mitochondrial dysfunction by stabilizing c-myc G-quadruplex DNA structure. Results indicated that phenanthroimidazole derivatives could act as promising anticancer agents.
研究领域:
药理学
·
肿瘤学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ONCOLOGY REPORTS
·
2020
·Vol. 44
·期 3
·927-938
·
IF 3.417
Songhui Zhou,Ruicheng Wang,Hong Xiao
The resistance of cancer cells to carboplatin restricts their efficacy in the clinical setting, and a solution to reverse the resistance is urgently required for the treatment of ovarian cancer. An increasing number of studies have found associations between obesity and the incidence, and mortality rates of female cancer. However, the association between adipocytes and the resistance of ovarian cancer has rarely been reported. Based on this, the present study first revealed the inductive effect of adipocytes on the resistance of ovarian cancer to carboplatin using in vivo and in vitro experiments. Subsequently, it was identified that the angiopoietin‑like 4 (ANGPTL4) secreted by adipocytes played a vital role in the resistance of ovarian cancer using bioinformatics analysis, cellular and molecular biological experiments, as well as forward and backward validation. The glycosylated ANGPTL4 protein could bind with integrin α5β1 on the surface of ovarian cancer cells; following which, it could activate the c‑myc/NF‑κB pathway and stimulate the expression of the antiapoptotic protein Bcl‑xL, as well as the ABC transporter family members ABCB1, ABCC1 and ABCG2. Thus, inducing the resistance of ovarian cancer to carboplatin. In conclusion, targeting the adipocyte‑derived ANGPTL4 combined with the application of carboplatin contributes to the clinical treatment for ovarian cancer.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSCIENCE REPORTS
·
2019
·Vol. 39
·期 1
·
IF 2.535
Chen Gang,Chen Weicheng,Ye Ming,Tan Weiqiang,Jia Bing
Neuroblastoma is the most common tumor in children, with a very poor prognosis. It is urgent to identify novel biomarkers to treat neuroblastoma, together with surgery, chemotherapy, and radiation. Human tripartite motif 59 (TRIM59), a member of the TRIM family, has been reported to participate in several human tumors. However, the exact role of TRIM59 in neuroblastoma is unknown. In the present study, real-time PCR and Western blot were used to measure mRNA and protein levels of TRIM59 in four neuroblastoma cell lines and in neuroblastoma tissues. Lentiviruses targeting TRIM59 were used to up/down-regulate TRIM59 expression levels. Cell Counting Kit-8 and Annexin-V/PI were used to analyze cell proliferation and apoptosis in neuroblastoma cell lines. Our data showed that TRIM59 knockdown inhibits cell proliferation while inducing apoptosis in SH-SY5Y and SK-N-SH neuroblastoma cell lines. TRIM59 knockdown up-regulated expression of Bax and Bim and down-regulated levels of Survivin, β-catenin, and c-myc. Interestingly, the inhibition of cell proliferation caused by TRIM59 knockdown could be blocked by LiCl, which is an agonist of Wnt/β-catenin signaling pathway. In contrast, TRIM59 overexpression could increase cell proliferation, up-regulate Survivin, β-catenin and c-myc, down-regulate Bax and Bim, and these effects could be blocked by XAV939, which is an inhibitor of Wnt/β-catenin signaling pathway. In addition, TRIM59 was up-regulated and positively related with β-catenin in neuroblastoma tissues. In conclusion, TRIM59 was up-regulated in neuroblastoma, and TRIM59 knockdown inhibited cell proliferation by down-regulating the Wnt/β-catenin signaling pathway in neuroblastoma.
研究领域:
肿瘤学
·
细胞生物学
·
分子生物学
✓ 已验证
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）