通讯机构：
Beijing Engineering Research Center of Livestock Products Quality and Safety Source Control, Nutrition and Health Research Institute, COFCO, Beijing, China
摘要：
Polysaccharides are considered to be promising candidates for non-viral gene delivery because of their molecular diversity, which can be modified to fine-tune their physicochemical properties. In this work, transcriptional activator protein (TAT) functionalized PEI grafted polysaccharide polymer (PRBP) was prepared by using rice bran polysaccharide as the starting material, and characterized by various methods. The potential of TAT functionalized PRBP (PRBP-TAT) as gene vector was studied in vitro, including DNA loading capacity, DNA protection ability and biocompatibility. The cell uptake and transfection efficiency of the PRBP-TAT/pDNA polyplexes were studied. The results showed that PRBP-TAT could completely condense DNA at N/P 2. The PRBP-TAT/pDNA polyplexes could protect DNA from degrading by DNase and were efficiently internalized by cells. Biocompatibility result showed that PRBP-TAT had no significant cytotoxicity and effect on cell proliferation. At low N/P ratios of 1-3.5, PRBP-TAT showed higher transfection efficiency than PEI30k and PEI30k-grafted rice bran polysaccharide. PRBP-TAT and PEI showed the highest transfection efficiency of 42.8% and 28.1% when pDNA is 2 microg and N/P ratio is 1.5, respectively, while PRBP showed the highest transfection efficiency of 37.3% at N/P 2.5. These results indicate that PTA is a promising candidate vector for safe and efficient gene delivery.
摘要：
Metal complexes, as a type of potential non-virus gene carriers, have gained much attention due to their properties of high charge density and unique three-dimensional structure. This study investigated the potential of polyethyleneimine (PEI)-modified rice bran polysaccharide-Fe(III) complex (PEI-PI) as a safe gene delivery system and explored the effect of Fe(III) on the efficiency of gene transfection mediated by PEI modified rice bran polysaccharide (PEI-P) and PEI-PI. Gel retardation assay was used to study the DNA binding and protection capability, MTT assay was performed to evaluate the biocompatibility, and PEI-PI complex-mediated EGFP gene transfection was studied in vitro. Results showed the PEI-PI could induce DNA condensation and protect DNA from degradation by DNase I at a low weight ratio (vector/DNA) of 2. At the same weight ratio, PEI exhibited the strongest DNA binding capability but PEI-PI exhibited the highest gene transfection efficiency among all carrier systems. Compared with the PEI-P + Fe(III) system, PEI-PI not only had a more significant capability to condense DNA but also presented higher gene transfection efficiency. Moreover, PEI-PI exhibited no obvious cytotoxicity to cells. This work provides a strategy for the design and development of gene vectors based on PI complexes. (C) 2019 Elsevier B.V. All rights reserved.
作者机构：
[Hu, Jian; Pan, Xianhua] Shanghai Inst Technol, Sch Perfume & Aroma Technol, Shanghai 201418, Peoples R China.;[Hu, Jian; Tian, Wei; Zhou, Ruolan; Zhang, Yuefan; Lv, Jiaguo; Zhu, Ju; Zheng, Canhui] Second Mil Med Univ, Sch Pharm, Shanghai 200433, Peoples R China.;[Tian, Wei] Wuhan Gen Hosp Guangzhou Command, Wuhan 430070, Hubei, Peoples R China.;[Zhou, Ruolan; Chen, Xin] Wuhan Polytech Univ, Sch Biol & Pharmaceut Engn, Wuhan 430023, Hubei, Peoples R China.
通讯机构：
[Xin Chen; Xianhua Pan; Canhui Zheng] S;School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China<&wdkj&>School of Pharmacy, Second Military Medical University, Shanghai 200433, China<&wdkj&>School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai 201418, China
通讯机构：
[Zhou, YJ; Zheng, CH] S;[Chen, Xin] W;Second Mil Med Univ, Sch Pharm, Shanghai 200433, Peoples R China.;Wuhan Polytech Univ, Sch Biol & Pharmaceut Engn, Wuhan 430023, Hubei, Peoples R China.
关键词：
Colchicine site inhibitors;Tubulin polymerization inhibitors;Antitumor activity;NCI-60 human tumor cell lines screen
摘要：
The colchicine site inhibitors (CSIs) displayed both antimitotic and vascular disrupting activities, therefore are promising potential antitumor agents. In this study, a series 1-phenyl-4,5-dihydro-2H-benzo[e]indazoles were found as new CSIs of which the bioactive configuration was locked. Among them, compounds C1 and C2 displayed the best activity, with tubulin polymerization IC50 of 3.4 and 1.5 mu M, and growth IC50 of low nanomolar concentrations against human colon cancer cell lines. In addition, compound C1 showed excellent broad-spectrum antitumor activity in the NCI-60 Human Tumor Cell Lines Screen, encouraging further study of this antitumor compound.
摘要：
Archaea and Bacteria have evolved different defence strategies that target virtually all steps of the viral life cycle. The diversified virion morphotypes and genome contents of archaeal viruses result in a highly complex array of archaea-virus interactions. However, our understanding of archaeal antiviral activities lags far behind our knowledges of those in bacteria. Here we report a new archaeal defence system that involves DndCDEA-specific DNA phosphorothioate (PT) modification and the PbeABCD-mediated halt of virus propagation via inhibition of DNA replication. In contrast to the breakage of invasive DNA by DndFGH in bacteria, DndCDEA-PbeABCD does not degrade or cleave viral DNA. The PbeABCD-mediated PT defence system is widespread and exhibits extensive interdomain and intradomain gene transfer events. Our results suggest that DndCDEA-PbeABCD is a new type of PT-based virus resistance system, expanding the known arsenal of defence systems as well as our understanding of host-virus interactions.
摘要：
Polysaccharides are capable of being modified by polycations to adjust their physical and chemical properties, which accordingly are considered as potential candidate materials for safe and efficient gene delivery. Here, we extracted and purified polysaccharides from rice bran, and their physicochemical properties were determined by various methods. Polyethyleneimine (PEI) modified rice bran polysaccharide (PRBP) was prepared by grafting RBP with low molecular weight PEI and the preparation was determined by FTIR. The potential of PRBP as a gene vector was systematically evaluated in vitro. The results show that PRBP can compact DNA and form PRBP/DNA polylexes with a particle size of 50-100 nm. The PRBP/DNA polylexes can protect DNA degradation from DNase I efficiently. Compared with PEI, higher transfection efficiency was achieved by the PRBP. At weight ratio of 3, the highest efficiency of gene transfection mediated by PRBP-2000 was obtained, which was 37.5% and significantly higher than PEI and commercial reagents (calcium phosphate cell transfection kit) and was closed to lipo6000. Furthermore, according to MTT results, the cytotoxicity of PRBP is much lower than that of PEI, especially for PEI2000. We hope these results will provide new strategy for rice bran polysaccharides development and application as biomaterials. (C) 2019 Elsevier B.V. All rights reserved.
摘要：
The effect on the intracellular reactive oxygen species (ROS) generation, and the antioxidant and cytotoxicity properties of rice bran polysaccharides (RBP) and RBP-metal complexes RBP-Fe(III), RBP-Cu, RBP-Zn and RBP-Ca, were evaluated using atomic absorption spectroscopy (AAS), scavenging activity assays, cell viability assay and fluorescence microscopy. The RBP-metal complexes were prepared using the hydrothermal method. The RBP-Fe(III) complexes were found to be potent scavengers for superoxide (O2-center dot) free radicals. The RBP alone and RBP-Ca complex showed high scavenging activity for 2,2-diphenyl-l-picrylhydrazyl (DPPH center dot) free radicals. In addition, the RBP-Fe(III) complex also showed good biocompatibility and lowered the intracellular ROS levels, while RBP alone, RBP-Zn and RBP-Ca complexes were observed to increase the intracellular ROS level. Our findings suggest that among the tested RBP-metal complexes, RBP-Fe(III) complex is a strong candidate as an antioxidant therapeutic. (C) 2018 Elsevier B.V. All rights reserved.
摘要：
Multiple myeloma (MM) is the second most common haematological malignancy. Almost all patients with MM eventually relapse, and most recommended treatment protocols for the patients with relapsed refractory MM comprise a combination of drugs with different mechanisms of action. Therefore novel drugs are in urgent need in clinic. Bcl-2 inhibitors and HDAC inhibitors were proved their anti-MM effect in clinic or under clinical trials, and they were further discovered to have synergistic interactions. In this study, a series of Bcl-2/HDAC dual-target inhibitors were designed and synthesized. Among them, compounds 7e-7g showed good inhibitory activities against HDAC6 and high binding affinities to Bcl-2 protein simultaneously. They also displayed good growth inhibitory activities against human MM cell line RPMI-8226, which proved their potential value for the treatment of multiple myeloma.
关键词：
Nickel;Particulate matter;Human exposure;Outdoor air
摘要：
Nickel is a widespread environmental contaminant, and it is toxic to humans in certain forms at high doses. Despite this, nationwide data on nickel in outdoor air particulate matter and human exposure to nickel through inhalation in China are limited. In the present study, 662 outdoor air samples from seven representative provinces such as Shanghai, Hubei, Hunan, Hebei, Guangdong, Yunnan, and Shanxi were collected between March 2013 and February 2014 and analyzed by inductively coupled plasma mass spectrometry. The concentrations of nickel in the air were in the range of 2.1-80.9 ng/m(3) (geometric mean: 14.4 ng/m(3)). In most areas, the concentrations of nickel were higher in winter and spring than those measured in summer and autumn. The daily intake (median) of nickel through inhalation of air particulate matter was estimated. Although the nickel concentrations in some air samples were high, inhalation of the air particulate matter accounted for a minor part of the total nickel intake; however, the adverse effects of human exposure to nickel through inhalation and its potential sources require more attention, particularly in Shanghai. This is a multiregional survey of nickel in outdoor air particulate matter in China. (C) 2018 Elsevier Ltd. All rights reserved.
摘要：
Background: Panacis Japonici Rhizoma (PJR) is one of the most famous Chinese medical herbs that is known for exhibiting potential anti-cancer effects. Purpose: This study aims to isolate and investigate the anti-cancer potential of saponins from PJR in ovarian cancer cells. Methods: The compounds were separated by comprehensive chromatographic methods. By comparison of the 1H- and 13C NMR data, as well as the HR-ESI-MS data, with the corresponding references, the structures of compounds were determined. MTT assay was performed to evaluate cell viability, along with flow cytometry for cell cycle analysis. JC-1 staining, Annexin V-PI double staining as well as Hoechst 33; 342 staining were used for detecting cell apoptosis. Western blot analysis was conducted to determine the relative protein level. Transwell assays were performed to investigate the effect of the saponin on cell migration and invasion and zymography experiments were used to detect the enzymatic activities. Results: Eleven saponins were isolated from PJR and their anti-proliferative effects were evaluated in human ovarian cancer cells. Chikusetsusaponin IVa methyl ester (1) exhibited the highest anti-proliferative potential among these isolates with the IC50 values at less than 10 mu M in both ovarian cancer A2780 and HEY cell lines. Compound 1 induced G1 cell cycle arrest accompanied with an S phase decrease, and down-regulated the expression of cyclin D1, CDK2, and CDK6. Further study showed that compound 1 effectively decreased the cell mitochondrial membrane potential, increased the annexin V positive cells and nuclear chromatin condensation, as well as enhanced the expression of cleaved PARP, Bax and cleavedcaspase 3 while decreasing that of Bcl-2. Moreover, compound 1 suppressed the migration and invasion of HEY and A2780 cells, down-regulated the expression of Cdc42, Rac, RohA, MMP2 and MMP9, and decreased the enzymatic activities of MMP2 and MMP9. Conclusion: These results provide a comprehensive evaluation of compound 1 as a potential agent for the treatment of ovarian cancer. (C) 2016 Elsevier GmbH. All rights reserved.
通讯机构：
[Chen, Wenli] H;Huazhong Agr Univ, State Key Lab Agr Microbiol, Wuhan 430070, Peoples R China.
关键词：
adsorption;mineral;N-acyl-homoserine lactone
摘要：
Bacterial interspecies and intraspecies communications are mediated by diffusible signaling molecules. In complex natural environments, the fluctuation of geochemical and physical conditions presents substantial challenges to the environmental fate of N-acyl-homoserine lactones. Although researchers have attempted to elucidate the influence of aquatic environmental parameters on bacterial QS signals, insufficient information is known regarding their interactions with soil. Thus, the adsorption of N-(3-oxododecanoyl) homoserine lactone on three common soil minerals (montmorillonite, kaolinite, and goethite) was investigated by performing batch studies coupled with Fourier-transform infrared spectroscopy and isothermal titration calorimetry. The adsorption isotherms of N-(3-oxododecanoyl) homoserine lactone on these minerals conformed to the Langmuir equation; the adsorbed N-(3-oxododecanoyl) homoserine lactone amount increased significantly as electrolyte concentration increased from 0.001 mol L−1 to 0.1 mol L−1. The adsorption of N-(3-oxododecanoyl) homoserine lactone on goethite was enhanced with increasing pH values; by contrast that on montmorillonite and kaolinite showed less dependence in the 6.0–8.0 pH range. Hydrogen bonding and hydrophobic interaction had important functions in these processes. This study provided insights into the distribution and diffusion of N-acyl-homoserine lactone in soil and associated environments.
作者机构：
[Wang, Chong-Qing; Zhou, You-Jun; Zheng, Can-Hui; Zhu, Ju; Jiang, Jun-Hang] Second Mil Med Univ, Sch Pharm, Shanghai 200433, Peoples R China.;[Chen, Xin] Wuhan Polytech Univ, Sch Biol & Pharmaceut Engn, Wuhan 430023, Peoples R China.;[Tang, Hui] Shandong Univ, Prov Hosp, Pharm, Jinan 250021, Peoples R China.;[Zhu, Kong-Kai] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China.
通讯机构：
[Zhou, You-Jun] S;Second Mil Med Univ, Sch Pharm, Shanghai 200433, Peoples R China.
关键词：
Benzyl-substituted flavone;Acidic rearrangement of benzyl group;Regioselectivity;Quantum chemical calculation
摘要：
The benzyl-substituted flavone compounds are rare in nature, while some of which have interesting biological activities. The total synthesis of benzyl-substituted flavone derivatives via the acidic rearrangement of benzyl groups in flavone benzyl ethers, and the complicated regioselectivity of the rearrangement were reported. The regioselectivity was proposed to be determined by the steric hindrance as well as the ease of electrophilic substitution reaction for benzyl cations at different positions of corresponding debenzylated flavone compounds.
