MOLECULES
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2017
·Vol. 22
·期 1
·171
·
IF 2.861
Xiangcong Wang,Maocai Yan,Qibao Wang,Huannan Wang,Zhengyang Wang,Jiayi Zhao,Jing Li,Zhen Zhang
Indole-2-carboxylic acid copper complex (ICA-Cu) was successfully prepared and characterized through elemental analysis, IR, UV-Vis,1H-NMR, TG analysis, and molar conductance, and its molecular formula was [Cu2(C9H6O2N)4(H2O)2]·2H2O. The binding ability of ICA-Cu to calf thymus DNA (CT-DNA) was examined by fluorescence spectrometry and the viscosity method. The results indicated that, upon the addition of increasing amounts of CT-DNA, the excitation and emission intensity of ICA-Cu decreased obviously and the excitation spectra shifted towards a long wavelength. ICA-Cu could displace ethidium bromide (EB) from the EB-DNA system, making the fluorescence intensity of the EB-DNA system decrease sharply; the quenching constantKSVvalue was 3.99 × 104M−1. The emission intensity of the ICA-Cu-DNA system was nearly constant, along with the addition of Na+in a series of concentrations. The fluorescence of the complex could be protected after the complex interacted with DNA. A viscosity measurement further supported the result that the ICA-Cu complex may interact with DNA in an intercalative binding mode. The antioxidant activities of ICA-Cu were evaluated by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, a hydroxyl radical (OH) scavenging assay, and a 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay. The ICA-Cu exhibited the highest inhibitory effects on the ABTS radical (94% inhibition at 60 µM), followed by OH and DPPH radicals (the degrees of inhibition being 71% and 56%, respectively). The in vitro cytotoxicity activity of ICA-Cu against two human breast cancer cell lines, MDA-MB-231 and MCF-7, was investigated by 3-[4,5-dimethyltiazol2-yl]-2.5-diphenyl-tetrazolium bromide (MTT) assay and cellular morphological analysis. The results showed that, upon increasing the concentration of ICA-Cu, an increase was observed in growth-inhibitory activity and the inhibition percentage were greater than 90% at 20 µM in both cell lines. Also, cellular morphological changes in the two cell lines agreed with the cytotoxicity results.Keywords:DNA-binding;antioxidant;anticancer;indole-2-carboxylicacid;copper(II) complexes
研究领域:
化学
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生物化学
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药理学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2017
·
IF 4.162
Yue Hu,Anchen Fu,Zhaoyi Miao,Xiaojing Zhang,Tianlin Wang,An Kang,Jinjun Shan,Dong Zhu,Wei Li
Although ligand fishing has been shown to be an efficient technique for the identification of bioactive components from complex mixtures such as natural products , it cannot be applied to biomedical image processing. Herein, a specific fluorescent ligand fishing combined with in situ imaging approach is presented for the identification of heat shock protein 90 (Hsp 90) inhibitors from complex matrixes, Curcuma longa L. , using N-terminus immobilized Hsp 90α functionalized InP/ZnS quantum dots embedded mesoporous nanoparticles ( i.e. Hsp 90α (NT)-FQDNs) as extraction sorbents and fluorescent tracer. The fished ligands were identified by liquid chromatography time-of-flight/mass spectrometry (LC-TOF/MS) and gas chromatography-mass spectrometry (GC-MS). Moreover, in situ imaging by confocal laser scanning microscopy (CLSM) was applied for evaluating the effect of fished-ligands on bioactivity-induced apoptosis morphologically in HeLa cells. MTT assay verified the bioactivity of the ligands and molecular docking results further provided convincing information to verify the feasible binding mode between ligands and protein. Twelve ligands as potential Hsp 90 inhibitors were ultimately fished and identified from Curcuma longa L. crude extracts. The proposed approach based on Hsp 90α functionalized nanocomposites is superior in the combination of highly specific screening efficiency and concurrent visual in situ imaging, which could have great promise for the development of other plant-derived Hsp 90 inhibitors, and providing a rapid and reliable platform for discovering biologically active molecules in natural products.
研究领域:
药理学
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生物化学
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分子生物学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2019
·
IF 6.044
Liru Zhang,Jie Liu,Xuejing Zheng,Ali Zhang,Xianliang Zhang,Keyong Tang
Herein the construction of a strong gelatin hydrogel is presented by using pullulan dialdehyde (PDA) as a macromolecular crosslinker. The resultant PDA crosslinked gelatin hydrogels (G-PDA) exhibit extremely high mechanical strength, manifested in the achieved optimal compressive stress of 5.80 MPa at 80% strain, which is up to 152 times higher than pure gelatin hydrogel. The G-PDA were characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The extent of crosslinking was determined by ninhydrin assay. The results suggested that the synergistic effect of dual-crosslinking, which is composed of short- and long-range covalent crosslinking and thermoreversible physical crosslinking, may played a key role in enhancing the load-bearing capacity of ensuing hydrogels. The swelling and enzymatic degradation of G-PDA are gradually limited with increasing PDA concentration. The result from MTT assay demonstrated that G-PDA is non-cytotoxic against MC3T3 cells, regardless of the concentrations of PDA.
研究领域:
材料科学
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生物医学工程
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生物材料
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
·
IF 6.51
Jiuheng Ruan,Chao Liu,Jiaqi Wang,Ting Zhong,Peng Quan,Liang Fang
This study sought to provide approach for evaluating and predicting the efficacy and safety of permeation enhancers on the basis of their kinetic distribution behavior in the skin dictated by physicochemical properties. Herein, the efficacy-safety regularity of eight permeation enhancers were studied with ex vivo skin permeation study, small-angle X-ray scattering, MTT assay, H&E staining, and in vivo skin erythema analysis, classifying into the following three categories: high enhancement–low irritation, medium enhancement–high irritation, and low enhancement–low irritation. These three modes were positively correlated with the distribution amount of permeation enhancers in the skin layers and verified by the in vitro tape-stripping study. The kinetic parameter, effective-safety index ( I ES ), was proposed to describe the regularity of enhancement effect tendency and irritation risk, and the relationship between I ES and physicochemical properties of permeation enhancers was analyzed with multiple regression analysis. According to the results of modulated temperature differential scanning calorimetry and dielectric spectrum, permeation enhancers with high lipophilicity and low polarity had I ES > 1, suggesting high enhancement effect and low irritation due to their higher affinity with the stratum corneum (SC) than with epidermis (EP). Permeation enhancers with medium lipophilicity and medium polarity exhibited 0 < I ES ≤ 1, showing medium enhancement effect and high irritation, as determined by their comparable affinity with the SC and epidermis (EP). However, permeation enhancers with low lipophilicity and high polarity had I ES → 0, demonstrating low enhancement effect and irritation, as indicated by their poor affinity with the SC. In summary, different physicochemical properties of permeation enhancers influenced their affinities with skin layers, resulting in their different enhancement effect and irritation potential. This study will provide a theoretical basis and criteria for evaluating and predicting the safety and efficacy of permeation enhancers, which will enable a more rational selection of permeation enhancers in the optimization of transdermal patches .
研究领域:
药剂学
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药理学
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生物物理学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Xiaoli Zhang,Shuhua Shan,Hanqing Li,Jiangying Shi,Yang Lu,Zhuoyu Li
A novel peroxidase (FMBP) was extracted and purified from foxtail millet bran in our previous study and it possessed excellent anti-colon cancer activity both in vitro and in vivo . However, the active fragment of FMBP responsible for the anti-colon cancer effects remains unclear. In present, three different truncated sequences of FMBP were designed and cloned into a plasmid vector (pMal-s). Three recombinant segments were successfully expressed in host strain Escherichia coli DH5α induced by IPTG (0.3 mM) at 37 °C for 4 h, respectively named MBP-FMBP-1, MBP-FMBP-2 and MBP-FMBP-3. MTT assay showed that only MBP-FMBP-2 possessed significant anti-colon cancer activity, and its anti-colon cancer activity was equivalent to FMBP. Further, the results showed that MBP-FMBP-2 significantly reversed the 5-Fu resistance in human colorectal cancer HCT-8/Fu cell through inhibiting cell proliferation, promoting cell apoptosis and increasing the intracellular accumulation of 5-Fu. RT-PCR and western blot assays showed that MBP-FMBP-2 also decreased the expression levels of multi-drug resistance protein 1 (MRP1), P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). These results indicate that MBP-FMBP-2 is the effective segment of FMBP which exhibits anti-colon cancer activity and has potential as an outstanding chemotherapeutic agent against colon cancer.
研究领域:
分子生物学
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癌症研究
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生物技术
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
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2016
·
IF 1.988
Lei Hou,Changfeng Gong,Yabin Zhu
In order to induce esophageal muscle cells’ orientation, the silicon wafer with prototype 1 and prototype 2 was designed. Prototype 1 has micro-channels of 200 µm width and 30 µm depth with 30 µm wide wall as the interval. Prototype 2 has channels of 100 µm width and 30 µm depth with a discontinuous wall which has 30 µm gap for each 100 µm channel. The poly(ester urethane) scaffolds with pattern prototype 1 and prototype 2 were fabricated using solution casting method and abbreviated as PU1 and PU2, respectively. Silk fibroin was grafted individually on PU1 and PU2 surface (PU1-SF, PU2-SF) using our previous protocol, aiming at improving scaffolds’ biocompatibility. The primary esophageal smooth muscle cell was seeded to evaluate the scaffolds’ cytocompatibility in vitro. Characterizations like MTT assay, immunocytochemistry, scanning electron microscope, and Western blotting were applied. After that, poly(ester urethane) scaffolds with double patterns, prototype 1 on the exterior, and prototype 2 in the lumen were implanted into the rabbit esophagous to test the regeneration of the muscle tissue. Results from these preliminary tests showed that the growth and differentiation of primary smooth muscle cells were promoted, but also the muscle tissue with endocircular and exolongitudinal architecture was in regenerating, against non-constitution in the animals without the patterned scaffold or with poly(ester urethane) plane membrane at the defaulted sites. This micro-channel pattern together with silk fibroin grafting and vascular endothelial growth factor coating greatly promoted the regeneration of esophageal muscle with normal histological structure.
研究领域:
生物医学工程
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组织工程
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再生医学
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DOI
PubMed
高影响因子
International Journal of Medical Sciences
·
2024
·Vol. 21
·期 15
·3018
·
IF 3.2
Qi Zhang,Chao Hu,Baoqing Qu,Cuiping Zhang,Longtao He
This work aimed to demonstrate the therapeutic effects of tumor microenvironment-responsive nanotherapeutic drugs targeting PSD95/Discs-large/ZO-1 domain (PDZ)-binding-kinase (PBK) in medulloblastoma Daoy and ONS-76 cells. The objective was to provide critical theoretical and practical foundations for the clinical adoption of tumor microenvironment-responsive nanotherapeutic drugs targeting PBK. The rabies virus glycoprotein (RVG) was utilized as a specific targeting molecule to form a tumor microenvironment-responsive nanocomplex, HPAA/RVG/PBK-siRNA, which incorporated glutathione (GSH) as a microenvironment stimulus factor within a hyperbranched polymer polyamide amine (HPAA). This nanocomplex also carried PBK-small interfering RNA (siRNA) for targeted PBK therapy. Characterization of HPAA, maleimide-polyethylene glycol-N-succinyl ester (MAL-PEG-NHS), HPAA-PEG, RVG, HPAA-RVG, and HPAA/RVG/PBK-siRNA was conducted using nuclear magnetic resonance spectroscopy, high-performance liquid chromatography (HPLC), dynamic light scattering, and transmission electron microscopy (TEM). Flow cytometry was employed to assess endocytosis and cell transfection of HPAA-RVG and HPAA/RVG/PBK-siRNA in Daoy and ONS-76 cells. The two cell lines were treated with HPAA/RVG/PBK-siRNA (HPAA/siRNA group), methoxy-PEG polyethylenimine (PEI-25k)/PBK-siRNA (PEI group), HPAA/RVG nanocarriers without PBK-siRNA (HPAA/RVG group), Dharmacon™ non-targeting siRNA (shNTC group), PBK-siRNA (Control group 1), AChR inhibitor (Control group 2), and GSH inhibitor (Control group 3), and compared with the control group (medium without any substances). Western blot analysis validated PBK expression levels (ELs) in various cell groups. Additionally, cell viability and proliferation were evaluated using methyl tetrazolium (MTT) assays and 5-Bromo-2'-deoxyuridine (BrdU) incorporation assays. The results revealed proton absorption peaks for HPAA at 2.78 ppm, 3.21 ppm, and 3.49 ppm, while RVG and HPAA-RVG exhibited characteristic absorption peaks at 23.653 min and 23.584 min, respectively, with peak areas of 4,856.6 and 6,927.3 for RVG. The nanoparticle sizes were 50-100 nm for HPAA-RVG and 100 nm for HPAA/RVG/PBK-siRNA, displaying spherical morphology and uniform size distribution. The average potential of HPAA-PEG was lower than that of HPAA ( P <0.05), and HPAA-RVG showed dramatically lower potential than HPAA ( P <0.001). At 8 hours, Daoy cells displayed higher endocytosis rates versus ONS-76 cells ( P <0.05). The transfection rates of HPAA-RVG in both ONS-76 and Daoy cells were higher than those of HPAA, with Daoy cells showing higher transfection rates than HPAA ( P <0.05). Under HPAA-RVG treatment, AChR levels in ONS-76 cells were significantly lower than those in Daoy cells ( P < 0.05). Compared to the control group, the PBK protein expression levels, cell survival rates, and the number of cells in the proliferative phase were significantly reduced in Control group 1, the PEI group, and the HPAA/siRNA group in both ONS-76 and Daoy cells, with the ONS-76 cells in the HPAA/siRNA group showing the lowest values among these groups ( P < 0.05). In summary, the findings indicated that the tumor microenvironment-responsive nanocomposite HPAA/RVG/PBK-siRNA selectively inhibited PBK expression in Daoy medulloblastoma cells, showcasing potential applicability in medulloblastoma therapy.
研究领域:
肿瘤学
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药学
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分子生物学
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纳米技术
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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）