Biomedical Optics Express
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2019
·Vol. 10
·期 4
·1581-1600
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IF 3.91
Ping Tang,Wendai Cheng,Xuanmeng He,Qinnan Zhang,Jing Zhong,Xiaoxu Lu,Shengde Liu,Liyun Zhong
Berberine (BBR), a traditional Chinese herb extract medicine, reveals some anticancer effects in leukemia, but it remains controversial about the molecular mechanism of BBR-induced leukemia cell apoptosis. In this study, combining Raman spectrum and spectral imaging, both the biochemical changes of BBR-induced Jurkat cell apoptosis and the precise distribution of BBR in single cell are presented. In contrast, we also show the corresponding results of Jatrorrhizine (JTZ) and Palmatine (PMT), two structural analogues of BBR. It is found that all three structural analogues can induce cell apoptosis by breaking DNA and the main action sites are located in phosphate backbone and base pair groups, but their action on cell cycle are different, in which BBR leads to the S phase arrest while JTZ and PMT are on the G2 phase arrest. Moreover, from the Raman spectra of DNA treated with different drugs, we find that the content of phosphate backbone and base pair groups in BBR-treated DNA are larger than those in JTZ or PMT. And this result reflects the strong capability of BBR breaking DNA backbone relative to JTZ or PMT, suggesting that the existence of methylene-dioxy on the 2, 3 units of A ring on the quinoline ring can greatly enhance the capability of BBR breaking DNA backbone, so the action effect of BBR-induced Jurkat cell apoptosis is better than those of PMT or JTZ. Further, by using Raman spectral imaging approach, we achieve the precise distribution of BBR in single cell, it is found that the receptor-mediated BBR targeting delivery based single-wall carbon nanotube and folic acid (SWNT/FA) reveals excellent performance in BBR targeting delivery relative to the conventional BBR diffusion approach. Importantly, these results demonstrate that Raman spectrum and spectral imaging should be a powerful tool to study the molecular mechanism of drug-induced cell apoptosis and evaluate the efficiency of drug delivery system.
研究领域:
生物医学
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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
Frontiers in Immunology
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2023
·
IF 7.3
Ben Yi,Shuai Zhang,Suying Yan,Yanfei Liu,Zhiqiang Feng,Tianhao Chu,Jun Liu,Wei Wang,Jun Xue,Chunze Zhang,Yijia Wang
Introduction Tumor-infiltrating T lymphocytes in the tumor microenvironment are critical factors influencing the prognosis and chemotherapy outcomes. As a Chinese herbal medicine, Marsdenia tenacissima extract (MTE) has been widely used to treat cancer in China. Its immunoregulatory effects on tumor-associated macrophages is well known, but whether it regulates tumor-infiltrating T-cell functions remains unclear. Method We collected 17 tumor samples from MTE-administered colorectal cancer patients, 13 of which showed upregulation of CD3+/CD8+ tumor-infiltrating T cells. Further in vitro and in vivo experiments were performed to investigate the regulatory effects of MTE on tumor-infiltrating T cells and immune escape of tumors. Results Under single and co-culture conditions, MTE inhibited TGF-β1 and PD-L1 expression in the colorectal cancer (CRC) cell lines HCT116 and LoVo. In Jurkat cells, MTE inhibited FOXP3 and IL-10 expression, increased IL-2 expression, but had no effect on PD-1 expression. These findings were confirmed in vitro using subcutaneous and colitis-associated CRC mouse models. MTE also increased the density of CD3+/CD8+ tumor-infiltrating T cells and exhibited considerable tumor-suppressive effects in these two tumor mouse models. Conclusions Our findings suggested that MTE inhibits the immune escape of cancer cells, a precipitating factor increasing the immune response of T lymphocytes.
研究领域:
肿瘤学
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免疫学
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药理学
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PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2023
·
IF 5.8
Xinyue Xing,Wanqing Zhong,Ping Tang,Qiao Tao,Xiaoxu Lu,Liyun Zhong
The novel histone deacetylase drug chidamide (CHI) has been proven to regulate gene expression associated with oncogenesis via epigenetic mechanisms . However, huge side effects such as non-targeting, poor intracellular accumulation and low nuclear entry efficiency severely restrict its therapeutic efficacy. Dual-targeted nanodrug delivery systems have been proposed as the solution. Herein, we developed a CHI-loaded drug delivery nanosystem based on Prussian blue (PB) nanocarrier , which combines surface-enhanced Raman scattering (SERS) tracking function with cancer cell/nuclear-targeted chemotherapy capability. With the property of background-free SERS mapping, PB nanocarriers can serve as tracking agents to localize intracellular CHI. The incorporation of targeted molecules specifically enhances the cancer cell/nuclear internalization and chemotherapeutic effects of CHI-loaded PB nanocarriers. In vitro cytotoxicity assay clearly shows that the constructed CHI-loaded PB nanocarriers have significant inhibitory on Jurkat cell proliferation . Furthermore, SERS spectral analysis of Jurkat cells incubated with the CHI-loaded PB nanocarriers reveals obvious features of cellular apoptosis: DNA skeleton fragmentation, chromatin depolymerization , histone acetylation, and nucleosome conformation change. Importantly, this CHI-loaded PB nanocarrier will provide a new insight for lymphoblastic leukemia targeted chemotherapy.
研究领域:
药学
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纳米技术
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癌症研究
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分子生物学
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生物医学工程
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Shuang Yue,Xiaotong Wang,Lei Wang,Jiajia Li,Yufeng Zhou,Yan Chen,Zeyang Zhou,Xiaodong Yang,Xiaofeng Shi,Song Gao,Zhongmin Wen,Xiaojun Zhu,Yan Wang,Shuang Yang
The Tn antigen, an immature truncated O-glycosylation, is a promising biomarker for cancer detection and diagnosis. However, reliable methods for analyzing O-GalNAcylation and complex O-glycosylation are lacking. Here, we develop a novel method, MOTAI, for the sequential analysis of O-glycosylation using different O-glycoproteases. MOTAI conjugates glycopeptides on a solid support and releases different types of O-glycosylation through sequential enzymatic digestion by O-glycoproteases, including OpeRATOR and IMPa. Because OpeRATOR has less activity on O-GalNAcylation, MOTAI enriches O-GalNAcylation for subsequent analysis. We demonstrate the effectiveness of MOTAI by analyzing fetuin O-glycosylation and Jurkat cell lines. We then apply MOTAI to analyze colorectal cancer and benign colorectal polyps. We identify 32 Tn/sTn-glycoproteins and 43 T/sT-glycoproteins that are significantly increased in tumor tissues. Gene Ontology analysis reveals that most of these proteins are ECM proteins involved in the adhesion process of the intercellular matrix. Additionally, the protein disulfide isomerase CRELD2 has a significant difference in Tn expression, and the abnormally glycosylated T345 and S349 O-glycosylation sites in cancer group samples may promote the secretion of CRELD2 and ultimately tumorigenesis through ECM reshaping. In summary, MOTAI provides a powerful new tool for the in-depth analysis of O-GalNAcylation and complex O-glycosylation. It also reveals the upregulation of Tn/sTn-glycoproteins in colorectal cancer, which may provide new insights into cancer biology and biomarker discovery.
研究领域:
癌症生物学
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糖生物学
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生物化学
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分子生物学
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临床诊断
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产品关联
DOI
PubMed
高影响因子
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