DALTON TRANSACTIONS
·
2014
·Vol. 43
·期 24
·9216-9225
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IF 4.097
Qiong Wu,Tianfeng Chen,Zhao Zhang,Siyan Liao,Xiaohui Wu,Jian Wu,Wenjie Mei,Yanhua Chen,Weili Wu,Lingli Zeng,Wenjie Zheng
Two arene Ru(II) complexes coordinated by 2-(3-methoxyphenyl)imidazole[4,5-f][1,10]phenanthroline, [(η6-RC6H5)Ru(m-MOPIP)Cl]Cl (R = H, 1; R = CH3, 2), have been prepared under microwave irradiation; the crystal structure of 2 exhibits a typical “piano stool” conformation, with bond angles for N1–Ru1–Cl1 86.02 (14)° and N2–Ru1–Cl1 84.51 (14)°. The Ru–C distance for the Ru atom bound to the benzene ring is about 0.2178(8) nm, and the average Ru–N distance for Ru atom to the two chelating N atoms is about 0.2092(4) nm. The evaluation of in vitro anticancer activities revealed that these synthetic Ru(II) complexes selectively inhibited the growth of HepG2 hepatocellular carcinoma cells, with low cytotoxicity toward LO2 human normal liver cells. The results demonstrated that the complexes exhibited great selectivity between human cancer and normal cells by comparing with the ligand m-MOPIP. Furthermore, complexes 1 and 2 could bind to c-myc G4 DNA in groove binding mode in promising affinity, and the insertion of the methyl groups in the arene ligand contributed to strengthen the binding affinity. This was also confirmed by molecular docking calculation and 1H NMR analysis which showed that both 1 and 2 can bind in the loop constructed by A6–G9 and G21–A25 base pairs in c-myc G4 DNA to block the replication of c-myc oligomer. Taken together, these results suggest that arene Ru(II) complexes display application potential as small molecule inhibitors of c-myc G4 DNA.
研究领域:
无机化学
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药物化学
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癌症研究
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DNA相互作用
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Yulu Yang,Rui Chen,Yi Gong,Weihu Yang,Ke Li,Wuzhe Fan,Shuangquan Gou,Pengfei Gao,Tingting He,Kaiyong Cai
Diffuse large B-cell lymphoma (DLBCL) is a systemic hematological malignancy. Herein, through whole exome sequencing (WES), we found that DLBCL genome changes and expression characteristics are associated with various immune cells . Lenalidomide (Len) is a leading candidate for the immunomodulatory treatment of multiple myeloma in the clinic. Inspired by lenalidomide as an immunomodulatory drug for the treatment of multiple myeloma, we constructed a multifunctional nanoplatform with therapeutic and imaging properties for DLBCL by co-loading lenalidomide and dexamethasone (Dex) with upconversion nanoparticles using a GSH-sensitive linker (named as UCNPs-Len-Dex). In vitro cell experiments proved that the UCNPs-Len-Dex had good biocompatibility and obvious antitumor efficacy. UCNPs-Len-Dex also exhibited excellent anti-tumor efficacy and imaging properties in vivo . RNA sequencing showed that UCNPs-Len-Dex targeted and activated the E3 ligase of CRBN, resulting in IKZF1/3 degradation, which inhibited MYC/BCL6-positive DLBCL and maintained the stability of the immune microenvironment . Therefore, this study provided a new monitoring and therapeutic synergetic strategy for DLBCL.
研究领域:
肿瘤学
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血液学
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纳米技术
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免疫治疗
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分子生物学
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DOI
PubMed
高影响因子
MYCOSES
·
2026
·Vol. 69
·期 4
·e70176
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IF 3.4
Mingjing Wei,Jian Guo,Li Li,Junhao Zhu,Yuyuan Xue,Guo Chen,Fan Yang,Wenjuan Wu,Min Zhu
Background Candida auris is a globally emerging multidrug-resistant fungus. Its dissemination is driven by patient movement and asymptomatic carriers. However, molecular epidemiological studies linking imported cases to local strains in large metropolitan areas remain limited. Objectives To analyse the molecular epidemiology and resistance mechanisms of 33 clinical isolates in Shanghai and propose an integrated infection control strategy tailored to metropolitan healthcare settings. Methods Isolates from 19 patients were identified via MALDI-TOF MS and sequencing. Antifungal susceptibility and biofilm formation were assessed. Environmental contamination was evaluated using PCR. Whole-genome sequencing (WGS) was employed to identify resistance mutations and perform phylogenetic analysis. Results All 33 isolates were fluconazole-resistant. Resistance to amphotericin B and echinocandins was observed in 9 and 4 isolates, respectively. All echinocandin-resistant strains harboured the Fks1-S639F mutation. Phylogenetic analysis revealed that Clade III (South African clade) was the dominant lineage. Colonisation was concentrated in the urinary tract and inguinal regions, while bedside tables were identified as key environmental reservoirs. All strains exhibited strong biofilm-forming capacity. Conclusions ICU patients serve as primary reservoirs, with transmission driven by interregional movement. The distinct colonisation patterns and environmental hotspots provide specific targets for screening. Integrating PCR-based environmental monitoring with culture methods constitutes an effective strategy. These findings underscore the need for a standardised protocol integrating molecular diagnostics to optimise infection control in urban hospitals.
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DOI
PubMed
高影响因子
MYCOSES
·
2018
·Vol. 62
·期 5
·466-474
·
IF 2.793
Yangmin Gao,Ping Zhan,Ferry Hagen,Steph B. J. Menken,Jiufeng Sun,Ali Rezaei-Matehkolaei,Sybren de Hoog
Summary Trichophyton schoenleinii is an anthropophilic dermatophyte usually causing tinea favosa. Only few studies have provided data on molecular epidemiology and antifungal profiles of this fungus due to its limited prevalence after 1950s. Forty-nine strains from Asia (n = 27), Africa (n = 10), Europe (n = 10) and from unknown regions (n = 2) were analysed with amplified fragment length polymorphism fingerprinting (AFLP) to reveal intraspecific genetic diversity in this dataset. Amplified fragment length polymorphism fingerprinting genotyping revealed five clusters which did not correspond to geographic origins or clinical characteristics. Additionally, in vitro antifungal susceptibility to seven antifungals was provided for all strains. Terbinafine, ketoconazole, miconazole and itraconazole proved to be the most effective drugs, followed by griseofulvin. No correlation between genotypes and differences in antifungal susceptibility was observed. It is concluded that the AFLP groups are lineages within a single species.
研究领域:
医学真菌学
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流行病学
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药理学
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PubMed
高影响因子
MYCOSES
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2020
·Vol. 63
·期 11
·1215-1225
·
IF 3.575
Tiantian Pan,Xiaojing Liu,Chengcheng Liu,Jiao Li,Wenpeng Ma,Yannan Qin,Yunru Chen,Shumei Lin,Feng Ye
Background Current available treatment modes against dermatophytoses are often tedious and sometimes unsatisfactory. As an emerging and promising approach, antimicrobial photodynamic therapy (aPDT) attracts much attention in the treatment of superficial or localised infections. Objectives This work investigated the photodynamic efficacy and effects of haematoporphyrin monomethyl ether (HMME) on microconidia of Trichophyton rubrum in vitro. Methods The photodynamic killing efficacy of HMME on microconidia of two T rubrum strains was assessed by MTT assay. The effects of HMME-mediated aPDT on the growth of T rubrum and cellular structure of microconidia were also investigated. Confocal laser scanning microscopy (CLSM) and flow cytometry were employed to study the intracellular localisation of HMME and generation of reactive oxygen species (ROS). Results HMME showed no obvious toxicity in the dark, but after light irradiation it inactivated the T rubrum microconidia in a light energy dose-dependent manner, and inhibited the growth of T rubrum . CLSM demonstrated that HMME initially bound to the cell envelop and entered into the cell after light irradiation. HMME-mediated aPDT also damaged the cell cytoplasm and increased the accumulation of intracellular ROS, resulting in cell death. Conclusions The results suggested that HMME-mediated aPDT had potential to be used in the treatment of superficial infections caused by T rubrum .
研究领域:
医学
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微生物学
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DOI
PubMed
高影响因子
Journal of Advanced Research
·
2025
·
IF 13
Shize Zhang,Yuang Chen,Nan Aa,Chen Xu,Tao Xie,Yi Wang,Tian Cheng,Mengqin Wang,Hong Yu,Xinqiang Ji,Song Zhao,Yaohui Wang,Jun Xiao,Yuan Xie,Guangji Wang,Jiye Aa
Introduction The repair of structural damage of the intestinal barrier is critical to rescue ulcerative colitis (UC), but there lacks effective targets currently. Objectives This study aims to explore mechanisms and identify potential targets for repairing the damaged intestinal barrier involved in UC. Methods Nontargeted metabolomic and transcriptomic analyses were utilized to characterize the metabolic features of DSS-induced colitis and identify potential therapeutic targets. Pantothenate kinase 3 (PANK3) was pharmacologically and genetically modulated to elucidate its mechanistic role. Chromatin immunoprecipitation and dual-luciferase reporter assays were employed to identify upstream regulators of PANK3, and PANK3 agonists were screened by high-throughput docking and further confirmed by in vitro and in vivo experiments. Results Metabolomic data indicated that perturbed metabolism involves pantothenate kinase. Clinical database, qPCR, WB, and immunohistochemical staining revealed a significant decrease of PANK3 in both patients and murine models of colitis. Pharmacological activation or overexpression of PANK3 restored the integrity of the intestinal barrier in UC mice, whereas PANK3 knockdown or inhibition exacerbated barrier dysfunction. PANK3 is negatively regulated by upstream c-Myc, and affects downstream, epithelial‒mesenchymal transition (EMT). In general, elevated c-Myc suppressed PANK3 transcription, promoted the EMT process and induced barrier disruption. The natural vitamin folic acid was identified as an agonist of PANK3, which could markedly improve the intestinal barrier in DSS-induced colitis. Conclusion The c-Myc-PANK3-EMT axis plays a critical role in preserving the structure and function of intestinal barrier. PANK3 is a potential target and folic acid is a candidate agonist of PANK3 to repair intestinal barrier in UC.
研究领域:
胃肠病学
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分子生物学
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免疫学
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代谢组学
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转化医学
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DOI
PubMed
高影响因子
Nature Communications
·
2025
·
IF 15.7
Xinyi Wan,Haonan Fan,Zhuoning Li,Yixuan Du,Yu Liu,Weiwu Zeng,Zhongxing Sun,Juejia Shao,Junqi Jia,Yanjun Zhang,Dong Fang
DNA topology is critical for regulating transcription and maintaining cellular homeostasis. Z-DNA is a left-handed DNA helix in regions with high transcriptional activity. Its physiological function remains poorly understood. Here, we demonstrate that oncoprotein MYC induces the formation of Z-DNA by recruiting the chromatin remodeler FACT, independent of RNA Polymerase II activity. FACT facilitates Z-DNA formation by remodeling H2A/H2B dimers within intact nucleosomes. Additionally, the phosphorylation of FACT regulates its liquid-liquid phase separation, promoting its efficient recruitment to chromatin by MYC. Through a genome-wide analysis and characterization of engineered Z-DNA promoters, we found that Z-DNA directly facilitates the loading of RNA Polymerase II, thereby promoting transcriptional activity. This study elucidates the molecular mechanisms of Z-DNA dynamics and emphasizes its functional importance in transcriptional regulation, providing insights into the role of left-handed DNA structures in chromatin biology and MYC-driven cancer. Z-DNA forms at highly active genes, but its function is unclear. Here, the authors show that MYC recruits FACT to promote Z-DNA formation within nucleosomes, enabling RNA Polymerase II loading and enhancing transcription, revealing a mechanistic role for Z-DNA in MYC-driven regulation.
研究领域:
分子生物学
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肿瘤学
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表观遗传学
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染色质生物学
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转录调控
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癌症机制
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DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-20
·
IF 14.7
Bi Guoshu,Liang Jiaqi,Bian Yunyi,Shan Guangyao,Huang Yiwei,Lu Tao,Zhang Huan,Jin Xing,Chen Zhencong,Zhao Mengnan,Fan Hong,Wang Qun,Gan Boyi,Zhan Cheng
Targeting ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal overload of lipid peroxides, in cancer therapy is impeded by our limited understanding of the intersection of tumour’s metabolic feature and ferroptosis vulnerability. In the present study, arginine is identified as a ferroptotic promoter using a metabolites library. This effect is mainly achieved through arginine’s conversion to polyamines, which exerts their potent ferroptosis-promoting property in an H 2 O 2 -dependent manner. Notably, the expression of ornithine decarboxylase 1 (ODC1), the critical enzyme catalysing polyamine synthesis, is significantly activated by the ferroptosis signal——iron overload——through WNT/MYC signalling, as well as the subsequent elevated polyamine synthesis, thus forming a ferroptosis-iron overload-WNT/MYC-ODC1-polyamine-H 2 O 2 positive feedback loop that amplifies ferroptosis. Meanwhile, we notice that ferroptotic cells release enhanced polyamine-containing extracellular vesicles into the microenvironment, thereby further sensitizing neighbouring cells to ferroptosis and accelerating the “spread” of ferroptosis in the tumour region. Besides, polyamine supplementation also sensitizes cancer cells or xenograft tumours to radiotherapy or chemotherapy through inducing ferroptosis. Considering that cancer cells are often characterized by elevated intracellular polyamine pools, our results indicate that polyamine metabolism exposes a targetable vulnerability to ferroptosis and represents an exciting opportunity for therapeutic strategies for cancer.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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DOI
PubMed
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.
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2026
·
IF 11
Yan Gao,Ji Liu,Jiahui Hu,Chuansheng Xu,Shiyu Mao,Chen Li,Xudong Yao,Shuo Shi
Prostate cancer (PCa) is the most prevalent malignancy in men, often progressing to a more refractory form castration-resistant prostate cancer (CRPC) after primary androgen deprivation therapy. Immunotherapy has brought new hope to PCa patients, but the immunosuppressive characteristics of PCa cells limit its efficacy. Cuproptosis, which can affect tumorigenesis, therapeutic resistance, and immune modulation has received significant attention recently. However, it is limited by insufficient copper ion (Cu 2+ ) concentration, hypoxia, and overexpression of glutathione (GSH) in tumors. To overcome these limitations, a targeted nanoplatform (CuS@MYC-PEG-FA) is fabricated to achieve a synergistic cuproptosis and immunotherapy. CuS@MYC-PEG-FA can not only promote reactive oxygen species (ROS) generation and Cu 2+ release, but also elicit a powerful antitumor immunity response. Meanwhile, the loaded c-MYC inhibitor (MYCMI-6) can reduce the expression of glutaminase and subsequently inhibit the generation of GSH, further sensitizing cells to cuproptosis effectively. Notably, cuproptosis combined with photothermal therapy (PTT) can turn the “cold” tumor properties of PCa into “hot” ones, leading to its sensitivity to anti-programmed death ligand 1 (anti-PD-L1) immunotherapy. The results show that the combination of CuS@MYC-PEG-FA and PD-L1 inhibitor treatment can significantly inhibit the development of PCa, providing a new strategy for the treatment of PCa.
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高影响因子
LIFE SCIENCES
·
2022
·
IF 6.78
Tianfeng Yang,Cheng Cheng,Rui Xu,Jian Huo,Xiujuan Peng,Yanbin Chen,Yonghong Liang,Zhiheng Su,Yanmin Zhang
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most common cause of cancer-related deaths. The WW-domain containing oxidoreductase (WWOX) protein suppresses carcinogenesis and its absence is closely related to aggressive HCC phenotypes. In this study, by using SPR analysis, cell viability assay and xenograft mice models, we found that albendazole (ABZ), a safe and effective anthelmintic drug, exhibited the binding affinity with WWOX protein and potential inhibition effect on HCC cells in vitro and in vivo . Overexpression and knockdown of WWOX confirmed that the suppression of HCC by ABZ. Flow cytometric analysis, western blotting analysis and Co-IP were conducted to study the mechanism of ABZ. Our data showed that ABZ regulated the interaction between WWOX and its binding proteins including p53 and C-MYC. Furthermore, ABZ triggered p53-induced intrinsic apoptosis and suppressed EMT-mediated migration by C-MYC/Fibronectin axis. In addition, ∆NP73 expression was significantly inhibited by ABZ, which further sensitized p53-induced intrinsic apoptosis and cell cycle arrest. In summary, ABZ could suppress the proliferation and migration of HCC cells by regulating WWOX-dependent signaling pathway.
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
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
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高影响因子
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