NEW JOURNAL OF CHEMISTRY
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2022
·Vol. 46
·期 25
·12034-12040
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IF 3.925
Zhenqing Yu,Xiang Li,Xiaofeng Lu,Yong Guo
The occurrence of numerous neurodegenerative diseases is associated with abnormal levels of butyrylcholinesterase (BChE). The development of a probe for the real-time detection of butyrylcholinesterase in vivo and in vitro is beneficial for the diagnosis of related diseases. In this study, we designed and synthesized a novel fluorescent probe CnN to detect BChE activity. The probe CnN has numerous excellent properties for the real-time visualization of BChE with an ultrafast response (5 min), low detection limit (LOD of 0.07969 U mL−1) and good specificity. CnN also has a large Stokes shift (113 nm) and low cytotoxicity. Based on the excellent performance of CnN, we performed the endogenous imaging of apoptosis in LO2 cells, which can be used to assess stress changes in butyrylcholinesterase in apoptotic cells.
研究领域:
生物化学
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分子生物学
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神经科学
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细胞生物学
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产品关联
DOI
高影响因子
Frontiers in Chemistry
·
2022
·
IF 5.545
Zhu Jun,Kong Ling-Qi,Chen Qin-Hua,Li Bin,Wu Lun,Ran Feng-Ying,Ke Li-Na,Zeng Xiao-Hua,Wang Hong-Mei
Marine alkaloids have novel structures and antitumor activities. Therefore, we synthesized rhopaladins’ analogs from marine alkaloids rhopaladins A-D and modified their structures to synthesize 4-benzylidene-5-pyrrolidone derivatives. Among the compounds, (2E, 4E)-4-(4-chlorobenzylidene)-2-(4-chlorostyryl)-N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide (RPDPRH) has high efficiency and less hepatotoxicity, with IC50 values of 4.66, 6.42, 17.66, 15.2, 12.36, 22.4, and 243.2 μM in vitro anti-proliferative activity testing against cervical cancer C-33A, CaSki, SiHa, and HeLa cells, human hepatocarcinoma HepG2 and 7402 cells, and human normal liver LO2 cells, respectively. In particular, RPDPRH has similar activity to cisplatin on human hepatocarcinoma cells, and cisplatin served as a positive control in our study. Next, the apoptosis of HepG2 and 7402 cells induced by RPDPRH at different concentrations was detected by Annexin V/PI flow cytometry. Moreover, the expression of apoptotic proteins was detected by Western blot analysis. Finally, the results showed that RPDPRH could induce apoptosis of hepatocarcinoma cells by regulating Bax and Bcl-2 expressions. In summary, our results indicate that RPDPRH has the potential to serve as an antitumor agent and plays a significant role in future studies.
研究领域:
药理学
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肿瘤学
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药物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
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2022
·
IF 1.61
Wei-Wei Ye,Xiang-Ying Meng,Qian Zhao,Jian-Yang Chen,Cong Liu,Feng Chen,Yong Zhou,Yi Wang
Echinacoside (ECH) is the main compound of Cistanche deserticola, which possesses antioxidant, antitumor, antifatigue, and anti-inflammatory properties. The present study investigated the protective effects of echinacoside on type 2 diabetes mellitus (T2DM)-induced injury in T2DM injury db/db mice model and insulin-resistant LO2 cell model. The results demonstrated that ECH probably alleviated T2DM-induced injury by mediating the AKT pathway, which provided a new direction for the treatment of T2DM-induced injury.
研究领域:
药理学
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糖尿病研究
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2020
·
IF 4.268
Ying Xie,Sen-Ling Feng,Chu-Tian Mai,Yan-Fang Zheng,Hui Wang,Zhong-Qiu Liu,Hua Zhou,Liang Liu
Background As dysregulation of immunometabolism plays a key role in the immunological diseases , dyslipidemia frequently observed in rheumatoid arthritis (RA) patients (60%) is associated with the disease activity and has been considered as the potential target of anti-inflammatory strategy. However, targeting of metabolic events to develop novel anti-inflammatory therapeutics are far from clear as well as the mechanism of dyslipidemia in RA. Purpose To explore the therapeutic potential and mechanisms of silybin again RA through the regulation of lipid metabolism . Methods Adjuvant-induced arthritis (AIA) rat model was used to examine the effects of silybin on modulating dysregulated lipid metabolism and arthritis. Metabolomics , docking technology, and biochemical methods such as western blots , qRT-PCR, immunofluorescence staining were performed to understanding the underlying mechanisms. Moreover, knock-down of LXRα and LXRα agonist were used on LO2 cell lines to understand the action of silybin. Results We are the first to demonstrate that silybin can ameliorate dyslipidemia and arthritis in AIA rats. Overexpression of LXRα and several key lipogenic enzymes regulated by LXRα, including lipoprotein lipase (LPL), cholesterol 7α and 27α hydroxylase (CYP7A, CYP27A), adipocyte fatty acid-binding protein (aP2/FABP4) and fatty acid translocase (CD36/FAT), were observed in AIA rats, which mostly accounted for dyslipidemia during arthritis development. Metabolomics, docking technology, and biochemical results indicated that anti-arthritis effects of silybin related to suppressing the up-regulated LXRα and abnormal lipid metabolism. Notably, activation of LXRα could potentiate cell inflammatory process induced by LPS through the regulation of NF-κB pathway, however, suppression of LXRα agonism by siRNA or silybin reduced the nuclear translocation of NF-κB as well as the induction of downstream cytokines, indicating LXRα agonism is the important factor for the arthritis development and could be a potential target. Conclusion The up-regulation of LXRα can activate lipogenesis enzymes to worsen the inflammatory process in AIA rats as well as the development of dyslipidemia, therefore, rectifying lipid disorder via suppression of LXRα agonism pertains the capacity of drug target, which enables to discover and develop new drugs to treat rheumatoid arthritis with dyslipidaemia.
研究领域:
免疫学
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药理学
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风湿病学
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代谢组学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ANALYST
·
2021
·Vol. 146
·期 15
·4934-4944
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IF 4.616
Yan Gao,Huaidong Peng,Lisi Li,Feng Wang,Jiang Meng,Hongling Huang,Shumei Wang,Paul C. H. Li,Yue Sun
It is urgent to obtain targeted drugs that selectively bind to pathological targets rather than physiological targets in the early stage of drug screening. G-Quadruplex has become one of the important targets in the development of anti-tumor drugs. However, drugs that target quadruplexes may also bind to dsDNA, which may lead to adverse reactions. In this study, a new three-phase laminar flow chip was constructed to enable the multi-components of a traditional Chinese medicine extract to dynamically and competitively bind with G-quadruplex DNA (on target) and double-stranded DNA (off target), so as to select high-efficiency and low-toxicity anti-tumor drugs. The results showed that there were five compounds in the extracts of Macleaya cordata seeds that exhibited obvious differences in binding to the two targets. Furthermore, the binding constants and modes of four identified alkaloids as they bound to two DNA targets were verified by fluorescence spectra and molecular docking methods. The toxicity to HepG2 and LO2 cells from the four alkaloids was also compared. The results showed that sanguinarine and chelerythrine could be used as candidate drugs with stronger binding to HT24 than DNA26. The chip can also be used for other types of double-target screening of other traditional Chinese medicine extracts or compound libraries.
研究领域:
药理学
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生物技术
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癌症研究
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分子生物学
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DOI
PubMed
高影响因子
DALTON TRANSACTIONS
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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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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2021
·
IF 7.514
Lele Yang,Sijia Wu,Jinchao Wei,Jiagang Deng,Xiaotao Hou,Erwei Hao,Lei Zhang,Peng Li
Glucose is a primary source of energy used in most organisms. Thus, development of reliable approaches to measure intracellular glucose uptake is an important research issue. 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy- d -glucose (2-NBDG), as a fluorescent glucose derivative, has been widely used to track intracellular glucose uptake by fluorescence imaging and measuring in mammalian cells. However, the avoid-less cross-interference of intrinsic autofluorescence background and tested fluorescent compounds limits its ability to provide trustworthy information on intracellular glucose uptake. By the extraction, separation and detection of 2-NBDG, a simple, sensitive and accurate HPLC-FLD method was established and validated for the measurement of intracellular glucose uptake in HepG2 cells. The developed method has been employed successfully to assess the glucose uptake activity of anti-diabetic drugs and fluorescent natural products. A fit-for-purpose partial validation was further performed for quantification and comparison of glucose uptake in AML12, LO2 hepatocytes, L6 myoblasts and 3T3-L1 preadipocytes.
研究领域:
分析化学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
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IF 5.6
Qiang Tang,Xiaoling Huang,Guangxing Liu,Hongran Huang,Jiayi Zhang,Jihua Wei,Yuanxun Gong,Qianli Tang,Kai Zhang,Xianjiu Liao
This study introduces a novel electrochemical biosensor for detecting Matrix Metalloproteinase-2 (MMP-2), a key biomarker in cancer diagnostics and tissue remodeling. The biosensor is based on a dual-amplification strategy utilizing T7 RNA polymerase isothermal amplification and CRISPR-Cas12a technology. The principle involves the release of a DNA template in the presence of MMP-2, leading to RNA synthesis by T7 RNA polymerase. This RNA activates CRISPR-Cas12a, which cleaves a DNA probe on the electrode surface, resulting in a measurable electrochemical signal.The biosensor demonstrated exceptional sensitivity, with a detection limit of 2.62 fM for MMP-2. This high sensitivity was achieved through the combination of transcriptional amplification and the collateral cleavage activity of CRISPR-Cas12a, which amplifies the signal. The sensor was able to detect MMP-2 across a wide dynamic range from 2 fM to 1 nM, showing a strong linear correlation between MMP-2 concentration and the electrochemical signal. In practical applications, the biosensor accurately detected elevated levels of MMP-2 in cell culture supernatants from HepG2 liver cancer cells, distinguishing them from normal LO2 liver cells. The use of an MMP-2 inhibitor confirmed the specificity of the detection. These results underscore the biosensor's potential for clinical diagnostics, particularly in early cancer detection and monitoring of tissue remodeling activities. The biosensor's design allows for rapid, point-of-care testing without the need for complex laboratory equipment, making it a promising tool for personalized healthcare and diagnostic applications.
研究领域:
生物传感器
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癌症生物学
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分子诊断
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电化学
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生物技术
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Jie Liu,Xinyu Li,Yushu Wu,Xinpeng Zhang,Xiangtai Wang,Lixia Yuan,Yanna Zhao,Min Liu
Imaging, silencing cancer-related microRNA, and chemotherapy-phototherapy (CTPT) combination therapy are crucial for cancer diagnosis and drug resistance overcoming. In this study, we designed a multifunctional DNA tetrahedron (MB-MUC1-TD) for the targeted delivery of combined daunorubicin (DAU) + toluidine blue O (TBO). The detection limit of miRNA-21 was determined to be 0.91 nM. The intercalation of DAU and TBO into MB-MUC1-TD was proved by spectroscopic and calorimetric methods. The thermodynamic parameters for the interactions of DAU and/or TBO with MB-MUC1-TD confirmed high drug loading. The first addition of TBO in the ternary system achieved a higher loading of both drugs and a more stable complex structure. Deoxyribonuclease I (DNase I) accelerated the release of DAU and/or TBO loaded in MB-MUC1-TD. Confocal laser scanning microscope demonstrated that MB-MUC1-TD exhibited good imaging ability for miRNA-21 to accurately identify cancer cells, and DAU/TBO was predominantly distributed within the nucleus of cancer cells. In vitro cytotoxicity showed better gene therapy efficacy of MB on MCF-7 cells, better biocompatibility of loaded DAU and TBO on LO2 cells, and stronger synergistic cytotoxicity of DAU + TBO on MCF-7/ADR cells. This study may establish a theoretical foundation for co-loading CTPT combination drugs based on multifunctional DNA nanostructures.
研究领域:
癌症研究
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纳米技术
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药学
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分子生物学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomed Research International
·
2019
·
IF 2.197
Dongyu Xie,Ping Zhou,Lin Liu,Wenjing Jiang,Haina Xie,Liang Zhang,Donghao Xie
Suitable content of iron is essential for human body, but iron overload is associated with many kinds of diseases including chronic liver damage. Recently, researchers find that iron overload promotes hepatocyte autophagy and apoptosis. However, the mechanism of iron overload in liver damage remains unclear. In this study, Lo2 cells were selected as the research object, iron dextran was a model drug, and astragaloside IV was a therapeutic drug to explore the role of iron overload. MTT assay and Annexin/PI double staining were used to measure cell viability and apoptosis. Ultrastructure was observed by transmission electron microscopy. The expression levels of apoptosis and autophagy-related proteins were determined by real-time PCR and Western Blot. The results showed that iron dextran could significantly inhibit Lo2 cell viability and increase the apoptosis rate, while astragaloside IV could reverse the inhibition of Lo2 cell viability and decrease the apoptosis rate. Transmission electron microscopy showed a significant increase in the number of autophagosomes after administration of iron dextran, and the application of astragaloside IV reduced the production of autophagosomes. LC3II/I was significantly upregulated in the model group but decreased in the astragaloside IV treatment group, and P62 showed the opposite trend. Iron dextran significantly upregulated the expression of Bax and downregulated Bcl2, while astragaloside IV reversed this trend. Finally, the inhibition of hepcidin caused by iron dextran was counteracted by astragaloside IV. In conclusion, the experimental results show that the iron overload model mainly induces excessive autophagy and apoptosis of hepatocytes, thus causing damage to hepatocytes, but astragaloside IV plays a certain therapeutic role in reversing this damage.
研究领域:
药理学
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肝病学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Inorganic Chemistry Frontiers
·
2019
·Vol. 6
·期 4
·1040-1049
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IF 5.934
Yi-Gang Wu,Dong-Bo Wang,Juan-Juan Hu,Xue-Qing Song,Cheng-Zhi Xie,Zhong-Ying Ma,Jing-Yuan Xu
The design, synthesis, crystal structures and in vitro biological assessment of three iron(III) complexes, namely [Fe(L1)2]Cl (1), [Fe(L2)2]·FeCl4 (2) and [Fe(L3)(HL3)2]·(FeCl4)2·(CH3OH) (3) (HL1 = N’-(4-oxothiazolidin-2-ylidene)picolinohydrazonamide, HL2 = 2-(2-(1-(pyridin-2-yl)ethylidene)hydrazono)thiazolidin-4-one, HL3 = 3-ethyl-2-(2-(1-(pyridin-2-yl)ethylidene)hydrazono)thiazolidin-4-one, are reported in this article. Single crystal X-ray diffraction revealed that all three complexes were mononuclear molecules, approaching a coordination polyhedron of octahedral geometry, in which the 4-thiazolidinone derivative ligands exhibited different coordination modes and conformations. Their interactions with DNA were investigated by UV–visible and fluorescence spectrometries, and by agarose gel electrophoresis. Results indicated that they presented efficient DNA binding propensities and cleavage activities. In vitro, the iron(III) complexes caused cell cycle arrest at the G1 phase in response to DNA damage, effectively inhibited the cyclinD1 expression and decreased the migration of HeLa cells with a lower wound-healing rate than that of the control. Complex 3 was the most sensitive to HeLa cancer cells, followed by 2 and 1. Attractively, the tested complexes demonstrated significantly enhanced selectivity index values determined for HeLa vs. LO2 normal cells compared with cisplatin, especially for complex 3, which was up to 13.94-fold. Unlike cisplatin, more complex 3 would accumulate in HeLa cancer cells compared with LO2 normal cells.
研究领域:
无机化学
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药物化学
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肿瘤学
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分子生物学
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生物化学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2020
·
IF 4.268
Dan Su,Zhou Liao,Binwei Feng,Tingting Wang,Baixi shan,Qiang Zeng,Jiagui Song,Yonggui Song
Background: P. chinensis saponins (PRS) are pentacyclic triterpenoid bioactive constituents from Pulsatilla chinensis (Bunge) Regel. In our previous study, PRS caused chronic liver injury (CLI) with the significant changes of lipid metabolites including sphingomyelin (SM) in serum after long-term administration. The SM in the hepatocytes membrane plays an indispensable role in maintaining cell membrane stability and regulating the extracellular and intracellular signal transduction . However, it is still unknown the pathway related to SM and the mechanism of CLI on hepatocyte. Purpose: The purpose of this study was to explore the hepatotoxicity mechanism of PRS in vivo and in vitro , to reveal the action of mechanism of SM and the pathway related to liver injury. Methods: SD rats were orally administered with PRS for 240 days and liver injury was evaluated by histological examinations. Metabolomics analysis was used to explore the liver metabolic pathway affected by PRS, and the expressions of related proteins were evaluated by western blots . To discover and elucidate the underlying mechanisms of metabolites changes induced by PRS at the cellular level, cellular morphology, MTT assays , western blots and cell membrane potential measurements were carried out using LO2 cells. Furthermore, the roles of SM and cholesterol (Chol) in hepatocyte injury were investigated individually in overload Chol and SM groups. Sphingolipid metabolic pathway related with ceramide/sphingomyelin (Cer/SM) balance was explored using cellular lipidomics and RT-PCR. Results: PRS gradually damaged the rat's liver in a time-dependent manner. The analysis of liver metabolism profiles showed that lipids metabolites were changed, including sphingolipid, bile acid , linoleic acid and fatty acid . We found that PRS induced apoptosis by interfering with bile acid-mediated sphingolipid metabolic pathway and Cer/SM balance in CLI. In in vitro experiments, PRS led to the increase of LDH leakage, depolarized cell membrane potential and caused cell membrane toxicity. Furthermore, PRS inducedG0/G1 phase cell cycle arrest in LO2 cells, simultaneously activated cellular extrinsic and intrinsic apoptosis pathways. PRS acted on SM and interfered with Cer/SM balance, which promote lipid metabolism dysregulation and apoptosis. Conclusion: PRS acted on SM to interfere Cer/SM balance on LO2 cell. Both in vivo and in vitro , PRS induced Cer/SM imbalance which promoted lipid metabolism disorder and apoptosis. Apoptosis and lipids changes gradually damaged the rats liver, and ultimately developed into CLI.
研究领域:
药理学
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毒理学
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细胞生物学
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代谢组学
✓ 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）