33 results on '"Qin, Lu"'
Search Results
2. Differential detection of immune cell activation by label-free radiation pressure force
- Author
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Daniel E. Barlow, Qin Lu, and Dhanya Haridas
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Lipopolysaccharides ,Forward scatter ,Cell ,Population ,02 engineering and technology ,Microscopy, Atomic Force ,Nitric Oxide ,Biochemistry ,Analytical Chemistry ,Nitric oxide ,Flow cytometry ,Interferon-gamma ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Electrochemistry ,medicine ,Animals ,Environmental Chemistry ,Interferon gamma ,education ,Spectroscopy ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,Innate immune system ,medicine.diagnostic_test ,021001 nanoscience & nanotechnology ,medicine.anatomical_structure ,chemistry ,Macrophages, Peritoneal ,Biophysics ,0210 nano-technology ,Cell activation ,medicine.drug - Abstract
Label-free radiation pressure force analysis using a microfluidic platform is applied to the differential detection of innate immune cell activation. Murine-derived peritoneal macrophages (IC-21) are used as a model system and the activation of IC-21 cells by lipopolysaccharide (LPS) and interferon gamma (IFN-γ) to M1 pro-inflammatory phenotype is confirmed by RNA gene sequencing and nitric oxide production. The mean cell size determined by radiation pressure force analysis increases slightly after the activation (4 to 6%) and the calculated percentage of population overlaps between the control and the activated group after 14 and 24 h stimulations are at 79% and 77%. Meanwhile the mean cell velocity decreases more significantly after the activation (14% to 15%) and the calculated percentage of population overlaps between the control and the activated group after 14 and 24 h stimulations are only at 14% and 13%. The results demonstrate that the majority of the activated cells acquire a lower velocity than the cells from the control group without changes in cell size. For comparison label-free flow cytometry analysis of living IC-21 cells under the same stimulation conditions are performed and the results show population shifts towards larger values in both forward scatter and side scatter, but the calculated percentage of population overlaps in all case are significant (70% to 83%). Cell images obtained during radiation pressure force analysis by a CCD camera, and by optical microscopy and atomic force microscopy (AFM) reveal correlations between the cell activation by LPS/IFN-γ, the increase in cell complexity and surface roughness, and enhanced back scattered light by the activated cells. The unique relationship predicted by Mie's theory between the radiation pressure force exerted on the cell and the angular distribution of the scattered light by the cell which is influenced by its size, complexity, and surface conditions, endows the cell velocity based measurement by radiation pressure force analysis with high sensitivity in differentiating immune cell activation.
- Published
- 2021
3. By inhibiting ADCY5, miR-18a-3p promotes osteoporosis and possibly contributes to spinal fracture
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Peng Xie, Tingting Han, Ben Shan, Xiaohua Zuo, Lei Wang, Jun Ma, Junli Dong, and Qin Lu
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0301 basic medicine ,Mrna expression ,Osteoporosis ,Biophysics ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Genes, Reporter ,Osteogenesis ,Spinal fracture ,medicine ,Humans ,In patient ,Molecular Biology ,Osteoblasts ,Base Sequence ,Chemistry ,Vertebral compression fracture ,Mesenchymal stem cell ,RNA ,Osteoblast ,Mesenchymal Stem Cells ,Cell Biology ,medicine.disease ,Cell biology ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Spinal Fractures ,Calcium ,Adenylyl Cyclases - Abstract
To investigate the influence of miR-18a-3p and ADCY5 on OP and osteogenic differentiation of human Mesenchymal stem cell (hBMSCs) and its possible mechanism. Samples were collected from osteoporotic patients with or without vertebral compression fracture, and without OP volunteers. MiR-18a-3p and ADCY5 mRNA expression levels in the tissue samples and hBMSCs during osteogenic differentiation were detected。MiR-18a-3p mimic and OE-ADCY5 were introduced into hBMSCs to research the effects of miR-18a-3p and ADCY5 on osteogenesis differentiation of hBMSCs. Dual luciferase reporter system and RNA pull-down were applied to determine whether ADCY5 was a target gene of miR-18a-3p. Compared with the control group, ADCY5 expression level was down-regulated in patients with OP-no-Frx and OP-Frx, but that of miR-18a-3p was up-regulated. In addition, ADCY5 increased during osteogenesis differentiation of hBMSCs, whereas miR-18a-3p did not. OE-ADCY5 significantly facilitated calcium deposition, ALP activity, osteoblast protein expression (OSX, ALP and EUNX2), miR-18a-3p mimic inhibited osteogenic differentiation, and partially reversed the effect of OE-ADCY5 on osteogenic differentiation. In general, miR-18a-3p targets ADCY5 to promote OP and may be involved in spinal fracturs.
- Published
- 2021
4. Flexible paper-based Ni-MOF composite/AuNPs/CNTs film electrode for HIV DNA detection
- Author
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Zhenjiao Shang, Xiaoya Hu, Qin Xu, Tong Su, Dangqin Jin, Yun Shu, and Qin Lu
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Materials science ,Composite number ,Biomedical Engineering ,Biophysics ,Nanoparticle ,Metal Nanoparticles ,02 engineering and technology ,Carbon nanotube ,Biosensing Techniques ,Electrochemistry ,01 natural sciences ,law.invention ,Redox indicator ,law ,Nickel ,Specific surface area ,Humans ,Electrodes ,Metal-Organic Frameworks ,Nanotubes, Carbon ,010401 analytical chemistry ,General Medicine ,DNA ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Membrane ,Chemical engineering ,Electrode ,Gold ,0210 nano-technology ,Biotechnology - Abstract
It is very important to develop a rapid, simple, low cost point-of-care (POC) method for the early diagnosis of pathogens. In this work, a flexible paper-based electrode based on nickel metal-organic framework (Ni-MOF) composite/Au nanoparticles/carbon nanotubes/polyvinyl alcohol (Ni–Au composite/CNT/PVA) was constructed to detect target human immunodeficiency virus (HIV) DNA by DNA hybridization using methylene blue (MB) as a redox indicator. The CNT/PVA and Ni–Au composite were deposited on the cellulose membrane by vacuum filtration and drop-coating method in turn to obtain Ni–Au composite/CNT/PVA (CCP) film electrode. Compared to the CNT/PVA film electrode, CCP film electrode makes a higher loading of the probe DNA for its large specific surface area and conjugated π-electron system that can provide hydrogen bond sources to achieve interactions between MOF and single-stranded DNA, which improves the sensitivity for detecting target DNA. The variation of peak current for MB molecules adsorbed onto DNA before and after hybridization with HIV DNA was monitored. Electrochemical results proved that the CCP film maintained stable electrochemical property even after bending 200 times or stretching under different strains from 0% to 20%. The flexible paper electrode showed excellent sensing performance with a linear range of 10 nM–1 μM and a low detection limit of 0.13 nM. The target HIV DNA was successfully detected even in complex serum samples using the flexible CCP film electrode. Therefore, the simple and inexpensive flexible paper-based MOF composite film electrode can also be utilized for other pathogens POC diagnosis.
- Published
- 2021
5. Terminal protection of peptides by interactions with proteins: A 'signal-on' peptide-templated gold nanocluster beacon for label-free protein detection
- Author
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Jian-Hui Jiang, Sili Yi, Qin-Lu Lin, Li-Juan Tang, and Qian Wen
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chemistry.chemical_classification ,Detection limit ,Signal Pathways ,Chemistry ,010401 analytical chemistry ,Metal Nanoparticles ,Peptide ,Biosensing Techniques ,02 engineering and technology ,021001 nanoscience & nanotechnology ,01 natural sciences ,Signal on ,Protein detection ,0104 chemical sciences ,Analytical Chemistry ,Spectrometry, Fluorescence ,Terminal (electronics) ,Biophysics ,Gold ,Peptides ,0210 nano-technology ,Selectivity ,Label free - Abstract
Characterization of the protein-peptide interactions are a critical for understanding the functions and signal pathways of proteins. Herein, a new finding of universal terminal protection that protein bind specifically with peptide and provide a protective coating to prevent peptide hydrolysis in the presence of peptidase. On the basis of this mechanism, we first reported a novel label-free fluorescence biosensor strategy that utilizes the protection of specific terminal protein on peptide-templated gold nanocluster (AuNCs) beacon for the detection of proteins. The fluorescence quenching of peptide-templated AuNCs can be effectively inhibited with increasing concentration of the specific protein, exhibiting a satisfactory sensitivity and selectivity toward protein with the detection limit of MDM2 and gp120 are 0.0019 U/mL and 0.0012 U/mL, respectively. The developed label-free fluorescence biosensor strategy provides new ideas to detect and screen protein for analyzing protein-peptide interaction in biomedical applications.
- Published
- 2021
6. Metal Phenolic Network‐Integrated Multistage Nanosystem for Enhanced Drug Delivery to Solid Tumors
- Author
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Jonathan F. Lovell, Xue-Liang Liu, Xin-Di Zhu, Hong-Zhuan Chen, Qin Lu, Xing Lai, Peng Sun, Yuhao Gao, Si-Cong Yang, Chao Fang, Xin Luan, Mao-Hua Zhu, and Yihang Yuan
- Subjects
Nanoparticle ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Biomaterials ,Mice ,Drug Delivery Systems ,In vivo ,Cell Line, Tumor ,Neoplasms ,medicine ,Animals ,Humans ,General Materials Science ,Chelation ,Doxorubicin ,Liposome ,Chemistry ,General Chemistry ,Mesoporous silica ,Photothermal therapy ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Drug Liberation ,Liposomes ,Drug delivery ,Biophysics ,Nanoparticles ,0210 nano-technology ,Biotechnology ,medicine.drug - Abstract
Metal-phenolic networks (MPNs) are an emerging class of supramolecular surface modifiers with potential use in various fields including drug delivery. Here, the development of a unique MPN-integrated core-satellite nanosystem (CS-NS) is reported. The "core" component of CS-NS comprises a liposome loaded with EDTA (a metal ion chelator) in the aqueous core and DiR (a near-infrared photothermal transducer) in the bilayer. The "satellite" component comprises mesoporous silica nanoparticles (MSNs) encapsulating doxorubicin and is coated with a Cu2+ -tannic acid MPN. Liposomes and MSNs self-assemble into the CS-NS through adhesion mediated by the MPN. When irradiated with an 808 nm laser, CS-NS liberated the entrapped EDTA, leading to Cu2+ chelation and subsequent disassembly of the core-satellite nanostructure. Photo-conversion from the large assembly to the small constituent particles proceeded within 5 min. Light-triggered CS-NS disassembly enhanced the carrier and cargo penetration and accumulation in tumor spheroids in vitro and in orthotopic murine mammary tumors in vivo. CS-NS is long circulating in the blood and conferred improved survival outcomes to tumor-bearing mice treated with light, compared to controls. These results demonstrate an MPN-integrated multistage nanosystem for improved solid tumor treatment.
- Published
- 2021
7. Tumor priming using metronomic chemotherapy with neovasculature-targeted, nanoparticulate paclitaxel
- Author
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Jonathan F. Lovell, Ying-Yun Guan, Chao Fang, Lin Zheng, Hong-Zhuan Chen, Peng Sun, Xin Luan, Yun-Ge Gao, Ya-Rong Liu, Hai-Jun Liu, Xiao Dong, Si-Cong Yang, Mei Zhao, and Qin Lu
- Subjects
0301 basic medicine ,Materials science ,Paclitaxel ,Cell Survival ,Biophysics ,Mice, Nude ,Priming (immunology) ,Angiogenesis Inhibitors ,Bioengineering ,Pharmacology ,Polyethylene Glycols ,Biomaterials ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Drug Delivery Systems ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Doxorubicin ,Cell Proliferation ,Tumor microenvironment ,Neovascularization, Pathologic ,Cell growth ,Metronomic Chemotherapy ,030104 developmental biology ,chemistry ,Mechanics of Materials ,Administration, Metronomic ,Lactates ,Ceramics and Composites ,Heterografts ,Nanoparticles ,Nanomedicine ,Female ,Nanocarriers ,Oligopeptides ,Neoplasm Transplantation ,medicine.drug - Abstract
Normalization of the tumor microenvironment is a promising approach to render conventional chemotherapy more effective. Although passively targeted drug nanocarriers have been investigated to this end, actively targeted tumor priming remains to be explored. In this work, we demonstrate an effective tumor priming strategy using metronomic application of nanoparticles actively targeted to tumor neovasculature. F56 peptide-conjugated paclitaxel-loaded nanoparticles (F56-PTX-NP) were formulated from PEGylated polylactide using an oil in water emulsion approach. Metronomic F56-PTX-NP specifically targeted tumor vascular endothelial cells (ECs), pruned vessels with strong antiangiogenic activity and induced thrombospondin-1 (TSP-1) secretion from ECs. The treatment induced tumor vasculature normalization as evidenced by significantly increased coverage of basement membrane and pericytes. The tumor microenvironment was altered with enhanced pO2, lower interstitial fluid pressure, and enhanced vascular perfusion and doxorubicin delivery. A "normalization window" of at least 9 days was induced, which was longer than other approaches using antiangiogenic agents. Together, these results show that metronomic, actively-targeted nanomedicine can induce tumor vascular normalization and modulate the tumor microenvironment, opening a window of opportunity for effective combination chemotherapies.
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- 2016
8. Impact of confinement on proteins concentrated in lithocholic acid based organic nanotubes
- Author
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Qin Lu, Youngchan Kim, Nabil Bassim, and Greg E. Collins
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Lithocholic acid ,Drug Compounding ,Green Fluorescent Proteins ,Analytical chemistry ,Molecular Dynamics Simulation ,Green fluorescent protein ,law.invention ,Diffusion ,Biomaterials ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Confocal microscopy ,law ,Microscopy ,Fluorescence Resonance Energy Transfer ,Particle Size ,Nanotubes ,Protein Stability ,Chemistry ,Water ,Fluorescence recovery after photobleaching ,Fluorescence ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Solutions ,Kinetics ,Luminescent Proteins ,Förster resonance energy transfer ,Microscopy, Fluorescence ,Biophysics ,Thermodynamics ,Lithocholic Acid ,mCherry ,Fluorescence Recovery After Photobleaching - Abstract
Organic nanotubes form in aqueous solution near physiological pH by self-assembly of lithocholic acid (LCA) with inner diameters of 20-40nm. The encapsulation of enhanced green fluorescent protein (eGFP) and resultant confinement effect for eGFP within these nanotubes is studied via confocal microscopy. Timed release rate studies of eGFP encapsulated in LCA nanotubes and fluorescence recovery after photobleaching (FRAP) indicate that the diffusive transport of eGFP out of and/or within the nanotubes is very slow, in contrast to the rapid introduction of eGFP into the nanotubes. By encapsulating two fluorescent proteins in LCA nanotubes, eGFP and mCherry, as a fluorescence resonance energy transfer (FRET) pair, the FRET efficiencies are determined using FRET imaging microscopy at three different protein concentrations with a fixed donor-to-acceptor ratio of 1:1. Förster theory reveals that the proteins are spatially separated by 4.8-7.2nm in distance inside these nanotubes. The biomimetic nanochannels of LCA nanotubes not only afford a confining effect on eGFP that results in enhanced chemical and thermal stability under conditions of high denaturant concentration and temperature, but also function as protein concentrators for enriching protein in the nanochannels from a diluted protein solution by up to two orders of magnitude.
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- 2015
9. Label-Free Detection of Bacillus anthracis Spore Uptake in Macrophage Cells Using Analytical Optical Force Measurements
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Sean J. Hart, Alex Terray, Colin G. Hebert, Qin Lu, and Tomasz A. Leski
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0301 basic medicine ,Optics and Photonics ,Cytochalasin D ,Optical force ,Analytical chemistry ,02 engineering and technology ,Analytical Chemistry ,03 medical and health sciences ,Mice ,Phagocytosis ,Lab-On-A-Chip Devices ,Microscopy ,Macrophage ,Animals ,RAW 264.7 Cells ,Spores, Bacterial ,Microscopy, Confocal ,biology ,Chemistry ,Lasers ,Macrophages ,fungi ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Fluorescence ,Spore ,Bacillus anthracis ,Luminescent Proteins ,030104 developmental biology ,Biophysics ,Nucleic acid ,0210 nano-technology - Abstract
Understanding the interaction between macrophage cells and Bacillus anthracis spores is of significant importance with respect to both anthrax disease progression, spore detection for biodefense, as well as understanding cell clearance in general. While most detection systems rely on specific molecules, such as nucleic acids or proteins and fluorescent labels to identify the target(s) of interest, label-free methods probe changes in intrinsic properties, such as size, refractive index, and morphology, for correlation with a particular biological event. Optical chromatography is a label free technique that uses the balance between optical and fluidic drag forces within a microfluidic channel to determine the optical force on cells or particles. Here we show an increase in the optical force experienced by RAW264.7 macrophage cells upon the uptake of both microparticles and B. anthracis Sterne 34F2 spores. In the case of spores, the exposure was detected in as little as 1 h without the use of antibodies or fluorescent labels of any kind. An increase in the optical force was also seen in macrophage cells treated with cytochalasin D, both with and without a subsequent exposure to spores, indicating that a portion of the increase in the optical force arises independent of phagocytosis. These results demonstrate the capability of optical chromatography to detect subtle biological differences in a rapid and sensitive manner and suggest future potential in a range of applications, including the detection of biological threat agents for biodefense and pathogens for the prevention of sepsis and other diseases.
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- 2017
10. Selective eradication of tumor vascular pericytes by peptide-conjugated nanoparticles for antiangiogenic therapy of melanoma lung metastasis
- Author
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Qin Lu, Hai-Jun Liu, Yun-Ge Gao, Chao Fang, Xin Luan, Ya-Rong Liu, Jian-Rong Xu, Chao Wang, Hong-Zhuan Chen, and Ying-Yun Guan
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Male ,Models, Molecular ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,media_common.quotation_subject ,Molecular Sequence Data ,Melanoma, Experimental ,Biophysics ,Angiogenesis Inhibitors ,Bioengineering ,Docetaxel ,Rats, Sprague-Dawley ,Biomaterials ,Mice ,Cell Movement ,In vivo ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Internalization ,Receptor ,Cell Proliferation ,media_common ,Mice, Inbred BALB C ,Neovascularization, Pathologic ,business.industry ,Melanoma ,Brain ,medicine.disease ,Immunohistochemistry ,Endocytosis ,Rats ,medicine.anatomical_structure ,Mechanics of Materials ,Apoptosis ,Drug delivery ,Ceramics and Composites ,Cancer research ,Nanoparticles ,Female ,Taxoids ,Pericyte ,Peptides ,Pericytes ,business ,medicine.drug - Abstract
Antiangiogenic cancer therapy based on nanoparticulate drug delivery systems (nano-DDS) is emerging as a promising new approach besides the proved molecular-targeted antiangiogenic agents. The current nano-DDS are restricted to the targeting to tumor vascular endothelial cells, but seldom efforts have been made to target the tumor vascular pericytes which are also actively involved in tumor angiogenesis. In this study, we developed a new nano-DDS, TH10 peptide (TAASGVRSMH) conjugated nanoparticles loading docetaxel (TH10-DTX-NP) that can target the NG2 proteoglycan highly expressed in tumor vascular pericytes, for the investigation of therapeutic efficacy in the mice bearing B16F10-luc-G5 melanoma experimental lung metastasis. The results demonstrated that TH10-DTX-NP achieved controlled drug release in PBS and the mixture of rat plasma and PBS (1:1, v/v), and exhibited favorable in vivo long-circulating feature. TH10 peptide conjugation facilitated the nanoparticle internalization in pericytes via the interaction between TH10 and NG2 receptor, leading to more inhibition of pericyte viability and migration. TH10-conjugated nanoparticles could accurately target the vascular pericytes of B16F10-luc-G5 lung metastasis, where DTX-induced pronounceable pericyte apoptosis. TH10-DTX-NP significantly prolonged the mice survival with no obvious toxicity, and this enhanced antitumor effect was closely related with the decreased pericyte density and microvessel density in the lung metastases. The present research reveals the potency and significance of targeting tumor vascular pericytes using nano-DDS in antiangiogenic cancer therapy.
- Published
- 2014
11. Suppression of colorectal cancer subcutaneous xenograft and experimental lung metastasis using nanoparticle-mediated drug delivery to tumor neovasculature
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Dehong Yu, Chao Fang, Xin Luan, Ya-Rong Liu, Fan Bai, Hong-Zhuan Chen, Mei Zhao, Ying-Yun Guan, Qin Lu, and Chao Wang
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Male ,Vincristine ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Necrosis ,Nanoparticle-Mediated Drug Delivery ,Colorectal cancer ,Biophysics ,Mice, Nude ,Bioengineering ,Umbilical vein ,Rats, Sprague-Dawley ,Biomaterials ,Mice ,Drug Delivery Systems ,Cell Movement ,Human Umbilical Vein Endothelial Cells ,medicine ,Animals ,Humans ,Lung ,Mice, Inbred BALB C ,business.industry ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Mechanics of Materials ,Apoptosis ,Toxicity ,Drug delivery ,Ceramics and Composites ,Cancer research ,Nanoparticles ,medicine.symptom ,Colorectal Neoplasms ,business ,Oligopeptides ,medicine.drug - Abstract
Antiangiogenic therapy is a validated approach for colorectal cancer (CRC) treatment. However, diverse adverse effects inevitably appear due to the off-target effect of the approved antiangiogenic inhibitors on the physiological functions and homeostasis. This study was to investigate a new tumor vessel targeting nanoparticulate drug delivery system, F56 peptide conjugated nanoparticles loading vincristine (F56-VCR-NP), for the effective treatment of CRC subcutaneous xenograft and experimental lung metastasis model. The controlled release behavior and in vivo pharmacokinetic profile of F56-VCR-NP were characterized. The tumor vessel targeting and antiangiogenic activity of F56-VCR-NP was evaluated in human umbilical vein endothelial cells (HUVEC, a classical cell model mimicking tumor vascular EC), subcutaneous human HCT-15 xenograft in immunodeficient nude mice, and experimental CT-26 lung metastasis model in immunocompetent mice. The therapeutic efficacy (animal survival and toxicity) was further investigated in the model of CT-26 lung metastasis in mice. F56-VCR-NP could achieve 30-day controlled drug release in PBS (pH 7.4) and exhibited favorable long-circulating feature in vivo. F56-VCR-NP could accurately target the CRC neovasculature and elicit nanoparticle internalization in the tumor vascular EC, where the antiangiogenic VCR-induced dramatic EC apoptosis and necrosis of CRC tissue. F56-VCR-NP significantly prolonged the mouse survival with no obvious toxicity (weight loss and anepithymia) in the CT-26 lung metastasis mice model, and this pronounced antitumor effect was closely related with the decreased microvessel density in the metastases. The present nanoparticle-based targeted antiangiogenic therapy may provide a new promising approach for the therapy of CRC and lung metastasis, which deserves further translational research.
- Published
- 2014
12. Rapamycin efficiently promotes cardiac differentiation of mouse embryonic stem cells
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Weiping Wang, Kangtao Ma, Yinan Liu, Chunyan Zhou, Qin Lu, Ping Chen, Yang Wang, Zhe Yang, Tao Li, Yuyao Tian, and Zhuqing Jia
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0301 basic medicine ,Biophysics ,Notch signaling pathway ,cardiomyocytes ,Biology ,Fibroblast growth factor ,Biochemistry ,Bone morphogenetic protein 2 ,Cell Line ,03 medical and health sciences ,Mice ,Animals ,Myocytes, Cardiac ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Research Articles ,Sirolimus ,FGF10 ,rapamycin ,mammalian target of rapamycin (mTOR) ,Wnt signaling pathway ,Cell Differentiation ,Mouse Embryonic Stem Cells ,Cell Biology ,embryonic stem cells ,Ascorbic acid ,Molecular biology ,Embryonic stem cell ,Antigens, Differentiation ,Cell biology ,030104 developmental biology ,Gene Expression Regulation ,embryonic structures ,Research Article - Abstract
To investigate the effects of rapamycin on cardiac differentiation, murine embryonic stem cells (ESCs) were induced into cardiomyocytes by 10−4 M ascorbic acid (AA), 20 nM rapamycin alone or 0.01% solvent DMSO. We found that rapamycin alone was insufficient to initiate cardiomyogenesis. Then, the ESCs were treated with AA and rapamycin (20 nM) or AA and DMSO (0.01%) as a control. Compared with control, mouse ESCs (mESCs) treated with rapamycin (20 nM) and AA yielded a significantly higher percentage of cardiomyocytes, as confirmed by the percentage of beating embryonic bodies (EBs), the immunofluorescence and FACS analysis. Rapamycin significantly increased the expression of a panel of cardiac markers including Gata4, α-Mhc, β-Mhc, and Tnnt2. Additionally, rapamycin enhanced the expression of mesodermal and cardiac transcription factors such as Mesp1, Brachyury T, Eomes, Isl1, Gata4, Nkx2.5, Tbx5, and Mef2c. Mechanistic studies showed that rapamycin inhibits Wnt/β-catenin and Notch signaling but promotes the expression of fibroblast growth factor (Fgf8), Fgf10, and Nodal at early stage, and bone morphogenetic protein 2 (Bmp 2) at later stages. Sequential treatment of rapamycin showed that rapamycin promotes cardiac differentiation at the early and later stages. Interestingly, another mammalian target of rapamycin (mTOR) inhibitor Ku0063794 (1 µM) had similar effects on cardiomyogenesis. In conclusion, our results highlight a practical approach to generate cardiomyocytes from mESCs by rapamycin.
- Published
- 2016
13. Nanoparticle-mediated drug delivery to tumor neovasculature to combat P-gp expressing multidrug resistant cancer
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Hong-Zhuan Chen, Qin Lu, Chao Fang, Dehong Yu, Mei Zhao, Ying-Yun Guan, Ya-Rong Liu, Chao Wang, Xin Luan, Fan Bai, and Fu-Qiang Ban
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Paclitaxel ,Colon ,Cell ,Biophysics ,Mice, Nude ,Apoptosis ,Bioengineering ,Adenocarcinoma ,Pharmacology ,Biomaterials ,Mice ,chemistry.chemical_compound ,Drug Delivery Systems ,Cell Line, Tumor ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Medicine ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Cytotoxicity ,P-glycoprotein ,Mice, Inbred BALB C ,biology ,business.industry ,Kinase insert domain receptor ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Vascular Endothelial Growth Factor Receptor-2 ,medicine.anatomical_structure ,chemistry ,Drug Resistance, Neoplasm ,Mechanics of Materials ,Drug delivery ,Ceramics and Composites ,biology.protein ,Nanoparticles ,Colorectal Neoplasms ,Peptides ,business - Abstract
Anticancer drug resistance is a common intractable obstacle in clinical cancer chemotherapy. Here, we hypothesize that antiangiogenic cancer therapy through the targeted delivery of antiangiogenic agents to the tumor endothelial cells (EC), not the resistant cancer cells, may have the potential of combating multidrug resistant cancer. The K237 peptide-conjugated paclitaxel loaded nanoparticles (K237-PTX-NP), which can target KDR receptors highly expressed in the tumor vasculature, were fabricated for this investigation and the human colorectal adenocarcinoma HCT-15 with naturally expressed P-gp on the cell surface was adopted as the resistant tumor model. The human umbilical vein endothelial cells (HUVEC, a classical cell model mimicking tumor EC) were much more sensitive, in the cytotoxicity and apoptosis test, to K237-PTX-NP than Taxol and non-targeted PTX-NP. The enhanced antiangiogenic feature of K237-PTX-NP can be ascribed to the active internalization mediated by the interaction of K237 and KDR specifically highly expressed on the HUVEC, and the significantly extended intracellular drug retention. The tumor vessel targeting of K237-PTX-NP led to increased nanoparticle accumulation in HCT-15 tumors, and more importantly, induced significant apoptosis of tumor vascular EC and necrosis of tumor tissues. Low dose paclitaxel formulated in K237-PTX-NP (1 mg/kg) achieved significant anticancer efficacy of inhibiting the growth of HCT-15 tumors, but the same efficacy could be only obtained with 8 fold dose paclitaxel (8 mg/kg) in Taxol plus XR9576, a potent P-gp inhibitor. The anticancer efficacy of K237-PTX-NP was well related with the improved antiangiogenic effect shown in the dramatically decreased intratumoral microvessel density and pronouncedly increased apoptotic tumor cells, and such approach did not lead to obvious toxicity in the mice. These results suggest that the nanoparticles targeting drug to tumor neovasculature may be a promising strategy for the treatment of multidrug resistant cancer.
- Published
- 2013
14. The use of nanoparticulate delivery systems in metronomic chemotherapy
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Fu-Qiang Ban, Ying-Yun Guan, Dehong Yu, Fan Bai, Chao Wang, Jonathan F. Lovell, Hong-Zhuan Chen, Chao Fang, Xin Luan, Ya-Rong Liu, Qin Lu, and Mei Zhao
- Subjects
Models, Molecular ,Biodistribution ,Biophysics ,Neovascularization, Physiologic ,Antineoplastic Agents ,Bioengineering ,Docetaxel ,Pharmacology ,Biomaterials ,Neovascularization ,Mice ,Drug Delivery Systems ,Bone Marrow ,Cell Movement ,Cell Line, Tumor ,Neoplasms ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Medicine ,Tissue Distribution ,Cell Proliferation ,Mice, Inbred BALB C ,Mucous Membrane ,Vascular Endothelial Growth Factor Receptor-1 ,business.industry ,Metronomic Chemotherapy ,Endocytosis ,Platelet Endothelial Cell Adhesion Molecule-1 ,Regimen ,Treatment Outcome ,Bone marrow suppression ,Mechanics of Materials ,Administration, Metronomic ,Drug delivery ,Toxicity ,Ceramics and Composites ,Cancer research ,Nanoparticles ,Female ,Taxoids ,medicine.symptom ,Peptides ,business ,medicine.drug - Abstract
Metronomic chemotherapy aiming at inhibiting tumor angiogenesis with conventional chemotherapeutics is a promising strategy for antiangiogenic cancer therapy. However, current metronomic chemotherapy mainly focuses on free small-molecule drugs, without any effort to achieve tumor-specific biodistribution, which may lead to long-term toxicity concerns. Metronomic chemotherapy using nanoparticulate drug delivery system (DDS) offers significant upside to reduce off-target side effects, decrease accumulated dose, and enhance the efficacy of tumor vessel targeting without compromising antitumor efficacy; but there has been a lack of thorough experimental data describing the targeted metronomic chemotherapy. Here, we develop a new nanoparticulate DDS, SP5.2 peptide conjugated, Flt-1 (VEGFR-1) targeted nanoparticles for docetaxel (SP5.2-DTX-NP), as a model for the investigation of targeted metronomic chemotherapy with respect to both antitumor efficacy and toxicity. The results demonstrate that metronomic SP5.2-DTX-NP exerts antitumor activity mainly through the antiangiogenic effect of docetaxel, which is specifically delivered into the tumor vascular endothelial cells through the nanoparticle internalization mediated by the interaction of SP5.2 and over-expressed Flt-1 receptors on tumor vessels. Moreover, the antitumor efficacy of targeted metronomic chemotherapy is better than that of the treatment with the DDS given in the maximum tolerated dose (MTD) regimen, which is shown in significantly prolonged mice survival and minimal drug-associated toxicity (bone marrow suppression, hematological toxicity, and mucosal injury of small intestine). The present research reveals and highlights the significance of targeted metronomic therapy with nanoparticulate DDS in antiangiogenic cancer therapy.
- Published
- 2013
15. Silencing Drp1 inhibits glioma cells proliferation and invasion by RHOA/ ROCK1 pathway
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Lifen Chen, Maojia Yin, Teng Wang, Xi Liu, Qin Lu, and Ying Liu
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0301 basic medicine ,Dynamins ,endocrine system ,Small interfering RNA ,RHOA ,Biophysics ,Tumor initiation ,Biology ,Biochemistry ,GTP Phosphohydrolases ,Mitochondrial Proteins ,03 medical and health sciences ,Cell Movement ,Glioma ,Cell Line, Tumor ,medicine ,Gene silencing ,Humans ,ROCK1 ,Gene Silencing ,Pseudopodia ,RNA, Small Interfering ,Molecular Biology ,Cytoskeleton ,Cell Proliferation ,rho-Associated Kinases ,Microvilli ,Cell growth ,Brain Neoplasms ,Cell Biology ,medicine.disease ,Actins ,Cell biology ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Tissue Array Analysis ,Case-Control Studies ,biology.protein ,Cancer research ,Immunohistochemistry ,rhoA GTP-Binding Protein ,Microtubule-Associated Proteins ,Signal Transduction - Abstract
Backgrounds Dynamin-related protein 1 (Drp1) is a newly discovered therapeutic target for tumor initiation, migration, proliferation, and chemosensitivity. In the present study, we aimed to examine the level of expression and distribution of DRP1 in glioma tissues and explore the concrete mechanism of DRP1 played in glioma. Methods Expression of DRP1 in glioma tissues was determined by immunohistochemistry staining. The DRP1 gene was knocked down using small interfering RNA, and was overexpressed using plasmids in glioma cells. To assess changes in cell function, in vitro assays for invasion and growth were applied. Protein expression was tested by using Western-blot method. Variation of F-actin in cells was analyzed using immunofluorescence staining. Interactions between proteins were determined by co-immunoprecipitation. Results The protein expression levels of DRP1 were significantly increased in glioma tissues compared to the normal brain tissues. Down-regulation of DRP1 decreased cell proliferation and invasion, and inhibited the formation of pseudopodias and microvillis. Moreover, a possible link between DRP1 and RHOA was confirmed when interactions between these two proteins were observed in the cells. Conclusions Our results demonstrated that silencing DRP1 regulated the cytoskeleton remodeling through inhibiting RHOA/ROCK1 pathway, and thus decreased the proliferation and invasion of glioma cells.
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- 2016
16. A novel fluorometric determination of melamine using cucurbit[7]uril
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Qin Lu, Juan Yang, Su-Fan Wang, Yunyou Zhou, and Min Liu
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Detection limit ,Mole ratio ,Measurement method ,Chromatography ,Chemistry ,Biophysics ,General Chemistry ,Condensed Matter Physics ,Biochemistry ,Binding constant ,Fluorescence ,Atomic and Molecular Physics, and Optics ,chemistry.chemical_compound ,Melamine - Abstract
Melamine is a toxic compound to both animals and human beings, and is connected to various diseases, such as kidney stones and bladder cancer. For the efficient detection of melamine, we have developed a novel sensitive cucurbit[7]uril (CB7) sensor with a detection limit at 0.20 μg mL −1 , and applied it to detect melamine in tainted milk. Fluorescence studies indicate that CB7 forms complex with melamine in a 1:1 mole ratio. The binding constant at various temperatures has been calculated and the interaction mechanism has been discussed based on molecular modeling result.
- Published
- 2010
17. Peptide-conjugated biodegradable nanoparticles as a carrier to target paclitaxel to tumor neovasculature
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Chao Fang, Qin Lu, Dehong Yu, Hong-Zhuan Chen, and Jing Xie
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Materials science ,Paclitaxel ,Polymers ,Polyesters ,Biophysics ,Biocompatible Materials ,Bioengineering ,Peptide ,Pharmacology ,Umbilical vein ,Polyethylene Glycols ,Biomaterials ,Mice ,chemistry.chemical_compound ,Drug Delivery Systems ,Cell Movement ,In vivo ,Neoplasms ,PEG ratio ,Animals ,Humans ,Lactic Acid ,Particle Size ,Cells, Cultured ,chemistry.chemical_classification ,Tube formation ,Aldehydes ,Drug Carriers ,Mice, Inbred BALB C ,Molecular Structure ,Neovascularization, Pathologic ,Antineoplastic Agents, Phytogenic ,chemistry ,Mechanics of Materials ,Drug delivery ,Ceramics and Composites ,Cancer research ,PEGylation ,Nanoparticles ,Female ,Peptides - Abstract
Antiangiogenic cancer therapy can be achieved through the targeted delivery of antiangiogenic agents to the endothelial cells of tumor neovasculature. In the present study, we developed a drug delivery system (DDS), nanoparticles conjugated with K237-(HTMYYHHYQHHL) peptides for tumor neovasculature targeting drug delivery. Paclitaxel, a chemotherapeutic agent with potent antiangiogenic activity, was used as a prototype drug. We synthesized the aldehyde poly(ethylene glycol)-poly(lactide) (aldehyde-PEG-PLA) block copolymer by ring opening polymerization. The nanoparticles loading paclitaxel (PTX-NP) were fabricated using the O/W emulsion and evaporation technique. K237 ligand, a peptide that can bind to the KDR receptors predominantly expressed on the surface of tumor neovasculature endothelial cells with high affinity and specificity and inhibit the VEGF-KDR angiogenic signal pathway, was conjugated to the aldehyde group of PEG chain using the N-terminal PEGylation technique. The K237 conjugated paclitaxel-loaded nanoparticles (K237-PTX-NP) had a hydrodynamic diameter of 150 nm. The K237 density on nanoparticle surface was 474 and the mean distance between two neighboring PEG chains linked to K237 peptide was 12 nm. The K237 conjugated nanoparticles could be significantly internalized by human umbilical vein endothelial cells (HUVEC) through the K237-KDR interaction, and this facilitated uptake led to the expected enhanced antiangiogenic activity shown by HUVEC proliferation, migration and tube formation compared to cells treated with the commercial formulation Taxol and PTX-NP. The long-circulating property and the K237 ligand of K237-PTX-NP warranted rapid, long-term, and accurate in vivo tumor neovasculature targeting, and thereafter the significant apoptosis of tumor neovasculature endothelial cells and necrosis of tumor tissues of MDA-MB-231 breast tumors implanted in female BLAB/c nude mice. This nanoparticulate DDS offers a new strategy for paclitaxel chemotherapy application and it could also be used to carry other chemotherapeutic drugs, genes, and proteins with antiangiogenic activity for antiangiogenic cancer therapy.
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- 2010
18. Delta-like ligand 4-targeted nanomedicine for antiangiogenic cancer therapy
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Chao Fang, Qin Lu, Hong-Zhuan Chen, Xin Luan, Hai-Jun Liu, Ya-Rong Liu, Yun-Ge Gao, Xiao Dong, Ying-Yun Guan, Chao Wang, and Si-Cong Yang
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Angiogenesis Inhibitors ,Pharmacology ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Drug Delivery Systems ,Subcutaneous Tissue ,Cell Movement ,Coumarins ,Neoplasms ,Medicine ,Tube formation ,education.field_of_study ,Mice, Inbred BALB C ,Neovascularization, Pathologic ,Intracellular Signaling Peptides and Proteins ,Endocytosis ,Drug Combinations ,Nanomedicine ,Paclitaxel ,Mechanics of Materials ,Drug delivery ,cardiovascular system ,Human umbilical vein endothelial cell ,Female ,Proteoglycans ,Collagen ,Cell Survival ,Molecular Sequence Data ,Biophysics ,Mice, Nude ,Bioengineering ,Antineoplastic Agents ,Biomaterials ,In vivo ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Amino Acid Sequence ,education ,Delta-like ligand 4 ,business.industry ,Cancer ,Membrane Proteins ,medicine.disease ,Xenograft Model Antitumor Assays ,Thiazoles ,chemistry ,Apoptosis ,Ceramics and Composites ,Nanoparticles ,Laminin ,business ,Peptides - Abstract
Tumor angiogenesis is a multistep process involved with multiple molecular events in cancer microenvironment. Several molecular-targeted agents aiming to suppress tumor angiogenesis have been successfully translated into cancer clinic. However, new strategies are still urgently desired to be excavated to overcome the poor response and resistance in some antiangiogenic therapies. Recently, Delta-like ligand 4 (Dll4) is identified to be specifically over-expressed on tumor vascular endothelial cells (EC), and the Dll4-Notch pathway serves as a critical regulator in the development and maintenance of tumor angiogenesis. The intensively up-regulated phenotype of Dll4 on the membrane of tumor vascular EC implies that Dll4 may act as a targetable address for drug delivery system (DDS) to achieve targeted antiangiogenic cancer therapy. Here, a nano-DDS, GD16 peptide (H2N-GRCTNFHNFIYICFPD-CONH2, containing a disulfide bond between Cys3 and Cys13) conjugated nanoparticles loading paclitaxel (GD16-PTX-NP), which can specifically target the angiogenic marker Dll4, was fabricated for the investigation of antiangiogenic therapeutic efficacy in human head and neck cancer FaDu (Dll4-negative) xenograft in nude mice. The results demonstrate that GD16-PTX-NP achieved controlled drug release and exhibited favorable in vivo long-circulating feature. GD16-PTX-NP exerted enhanced antiangiogenic activity in the inhibition of human umbilical vein endothelial cell (HUVEC) viability, motility, migration, and tube formation, and in the Matrigel plug model as well, which can be definitely ascribed to the active internalization mediated by the interaction of GD16 and the over-expressed Dll4 on EC. GD16-PTX-NP showed accurate in vivo tumor neovasculature targeting property in FaDu tumor, where the paclitaxel was specifically delivered into the tumor vascular EC, leading to significant apoptosis of tumor vascular EC and necrosis of tumor tissues. The antiangiogenic activity of GD16-PTX-NP significantly contributed to its in vivo anticancer efficacy in Fadu tumor; moreover, no overt toxicity to the mice was observed. Our research firstly presents the potency and significance of a Dll4-targeted nanomedicine in antiangiogenic cancer therapy.
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- 2014
19. Mechanisms of transcellular transport of wheat germ agglutinin-functionalized polymeric nanoparticles in Caco-2 cells
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Qingxiang Song, Meng Huang, Xiaoling Gao, Zhengxing Rong, Jun Chen, Xinguo Jiang, Hong-Zhuan Chen, Qin Lu, Bingxian Wu, Hong Qi, Lei Yao, and Quanyin Hu
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Wheat Germ Agglutinins ,Genetic Vectors ,Biophysics ,Bioengineering ,Biology ,Transport Pathway ,Polyethylene Glycols ,Biomaterials ,Microscopy, Electron, Transmission ,Coumarins ,Humans ,Transcellular ,Particle Size ,Polyglactin 910 ,Drug Carriers ,Microscopy, Confocal ,Endolysosome ,Cell biology ,Vesicular transport protein ,Transcytosis ,Mechanics of Materials ,rab GTP-Binding Proteins ,Paracellular transport ,Drug delivery ,Ceramics and Composites ,Nanoparticles ,Mutant Proteins ,Nanocarriers ,Caco-2 Cells - Abstract
Transcellular transport is essential for transmucosal and plasma-to-tissue drug delivery by nanoparticles, whereas its fundamental pathways have not been fully clarified. In this study, an in-depth investigation was conducted into the intracellular itinerary and the transcytosis pathway of wheat germ agglutinin-functionalized nanoparticles (WGA-NP) with various polymer architectures in the Caco-2 cell model. GFP-Rabs, Rab4, Rab5, Rab7, Rab11, GTPases served as key regulators of vesicular transport, and their mutants were transfected to Caco-2 cells respectively to determine the cellular itinerary of WGA-NP and the role of Rabs therein. Transcytosis inhibition experiments indicated that transcellular transport of WGA-NP (PEG 3000 -PLA 40000 formulation) happened in a cytoskeleton-dependent manner and majorly by means of clathrin-mediated mechanism. Intracellular transport, especially the endolysosome pathway was found largely contribute to the transcytosis of WGA-NP. WGA-NP with shorter surface PEG length (2000) resulted in higher cellular association and more colocalization with the clathrin-mediated transport pathway, while that with longer surface PEG length (5000) avoided the clathrin-mediated transport pathway but achieved higher transcytosis after 4 h incubation. WGA-NP with PLGA as the core materials obtained elevated lysosome escape and enhanced transcytosis after 2 h incubation. These findings provided important evidence for the role of polymer architectures in modulating cellular transport of functionalized nanocarriers, and would be helpful in improving carrier design to enhance drug delivery.
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- 2012
20. Selective Nuclear Transport of μ-Calpain
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Qin Lu and Ronald L. Mellgren
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Molecular Sequence Data ,Biophysics ,Digitonin ,Biology ,Biochemistry ,chemistry.chemical_compound ,Calcium-binding protein ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Molecular Biology ,Calpastatin ,Cell Nucleus ,Calpain ,Calcium-Binding Proteins ,Biological Transport ,Cell Biology ,Inhibitor protein ,Fluoresceins ,Cell biology ,Cytosol ,Cell nucleus ,medicine.anatomical_structure ,chemistry ,biology.protein ,Calcium ,Cattle ,Fluorescein ,Nuclear transport - Abstract
To study nuclear transport of purified calpains in an in vitro system, A431 cells were permeabilized with digitonin, and fluorescein-labeled calpains were introduced under conditions known to facilitate energy-dependent nuclear transport of proteins. Fluorescein-mu-calpain was transported into nuclei in an ATP-dependent fashion. The calpain-specific inhibitor protein, calpastatin, could not block mu-calpain translocation. Fluorescein-calpastatin and fluorescein-m-calpain were poorly transported at best. In the presence of rat liver cytosolic factors, accumulation of nuclear mu-calpain was maximum at approximately 1 microM Ca2+, and no transport was observed at 0.3 microM Ca2+. Rat erythrocyte and HeLa cell extracts supported transport in the absence of Ca2+.
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- 1994
21. Selecting temperature for protein crystallization screens using the temperature dependence of the second virial coefficient
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Qin-Qin Lu, Da-Chuan Yin, Yong-Ming Liu, Jun Liu, Si-Xiao Xie, Xikai Wang, and Yun-Zhu Guo
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Protein Structure ,Light ,Materials Science ,Biophysics ,Thermodynamics ,lcsh:Medicine ,Crystal growth ,Biochemistry ,Protein Chemistry ,law.invention ,law ,Macromolecular Structure Analysis ,Animals ,Scattering, Radiation ,Crystallization ,Solubility ,Particle Size ,lcsh:Science ,Biology ,Condensed-Matter Physics ,Multidisciplinary ,Crystallography ,Chemistry ,Physics ,lcsh:R ,Temperature ,Proteins ,Reproducibility of Results ,Computational Biology ,Genomics ,Chymotrypsinogen ,Solutions ,Refractometry ,Virial coefficient ,Models, Chemical ,Scientific method ,lcsh:Q ,Muramidase ,Structural Genomics ,Particle size ,Structural Proteins ,Protein crystallization ,Chickens ,Research Article - Abstract
Protein crystals usually grow at a preferable temperature which is however not known for a new protein. This paper reports a new approach for determination of favorable crystallization temperature, which can be adopted to facilitate the crystallization screening process. By taking advantage of the correlation between the temperature dependence of the second virial coefficient (B(22)) and the solubility of protein, we measured the temperature dependence of B(22) to predict the temperature dependence of the solubility. Using information about solubility versus temperature, a preferred crystallization temperature can be proposed. If B(22) is a positive function of the temperature, a lower crystallization temperature is recommended; if B(22) shows opposite behavior with respect to the temperature, a higher crystallization temperature is preferred. Otherwise, any temperature in the tested range can be used.
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- 2010
22. Polymer Translocation Through a Nanopore in an Interacting Membrane
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Wen-Qin Lu
- Subjects
chemistry.chemical_classification ,Nanopore ,Adsorption ,Membrane ,chemistry ,Polymer chemistry ,Drug delivery ,Biophysics ,Membrane channel ,Chromosomal translocation ,Polymer ,Nuclear pore - Abstract
The translocation of polymers through nanopores in membranes occurs in many biological processes, such as proteins transporting through membrane channels, DNA and RNA translocating across nuclear pores, and drug delivery. The mechanism of the translocations has attracted a lot of attention from experiments, analytical theories and computer simulations. In a recent simulation study, the influence of pore-polymer interaction on the polymer translocations was discussed. Some experiments implied that the interaction between polymers and membranes might play an important role in the polymer translocation through membranes. In the present work, we use dynamic Monte Carlo simulations to study the effects of interaction between polymer segments and the membrane on the translocation of polymer chains through an interacting membrane from cis side ( high concentration of chains ) to trans side (zero concentration ). Results show that there is a critical adsorption point ec of the interaction strength e. We find the translocation timeτ is almost independent from e fore ec, where n is the length of polymer chains. We estimate the value of the critical adsorption point ec is about −0.3, which is in good agreement with previous results in many literatures studying the adsorptions of polymers on surfaces.
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- 2010
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23. A simplified probe preparation for ELISA-based NF-kappaB activity assay
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Zuohua Feng, De-qin Lu, Hong Ye, Shiqiao Ye, Liping Zhu, Di-Xun Wang, Sheng-Yuan Liu, Qinghua Hu, and Si Jin
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Hybridization probe ,Ligand binding assay ,Biophysics ,NF-kappa B ,Endothelial Cells ,Enzyme-Linked Immunosorbent Assay ,Plasma protein binding ,Biology ,Biochemistry ,Molecular biology ,Cell Line ,DNA binding site ,Enzyme Activation ,chemistry.chemical_compound ,chemistry ,Transcriptional regulation ,Humans ,Biological Assay ,Oligomer restriction ,Oligonucleotide Probes ,Gene ,DNA ,Oligonucleotide Array Sequence Analysis - Abstract
Nuclear factor-kappaB (NF-kappaB) is critically involved in the transcriptional regulation of many genes and multiple biological and pathobiological processes. To efficiently monitor and to rapidly screen NF-kappaB transcriptional activity, an ELISA-based assay has been increasingly and successfully employed as a new method in a variety of cell lines and experimental models since its first demonstration and recent development. In the ELISA-based assay, NF-kappaB is captured by a double-stranded DNA probe pre-linked on multi-well plates. Typically, the DNA probe contains the double-stranded consensus binding sequence for active NF-kappaB and another double-stranded sequence linking the consensus binding sequence with the plate (linker sequence). Since nuclear factor has no binding activity with single-stranded DNA, we modified the probe construction as containing the double-stranded consensus binding sequence and a single-stranded-linker sequence. Our results show that this kind of probe is highly sensitive and specific for NF-kappaB activity assay, whereas the preparation of this kind of probe is much more convenient. A single-stranded-linker sequence may largely decrease nonspecific protein binding and thus increase the sensitivity of this assay.
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- 2005
24. Calpain inhibitors and serine protease inhibitors can produce apoptosis in HL-60 cells
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Qin Lu and Ronald L. Mellgren
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Proteases ,Serine Proteinase Inhibitors ,Leupeptins ,Proteolysis ,Biophysics ,Apoptosis ,HL-60 Cells ,Cycloheximide ,Cysteine Proteinase Inhibitors ,Biochemistry ,Serine ,chemistry.chemical_compound ,Coumarins ,medicine ,Humans ,Molecular Biology ,chemistry.chemical_classification ,Inhibitor of apoptosis domain ,Protein Synthesis Inhibitors ,medicine.diagnostic_test ,Calpain ,Cell biology ,Enzyme ,chemistry ,HtrA serine peptidase 2 ,Diazomethane ,Isocoumarins ,Oligopeptides - Abstract
Recent investigations indicate that proteolysis is an important event in generation of the apoptosis phenotype. Although various proteases have been suggested to be candidates for this proteolysis, the results from different laboratories are inconsistent. In the present studies, HL-60 cells were treated with cycloheximide to investigate proteases involved in apoptosis. The calpain inhibitors benzyloxycarbonyl-Leu-Leu-Tyr diazomethylketone and acetyl-Leu-Leu-Nle aldehyde were not capable of preventing apoptosis induced by cycloheximide. In the absence of cycloheximide, these two inhibitors could initiate apoptosis in HL-60 cells. The thiol protease inhibitor benzyloxycarbonyl-Leu-Val-Gly diazomethylketone neither prevented nor produced apoptosis. The serine protease inhibitors 3,4-dichloroisocoumarin (DCI) and tosyl-Phe chloromethylketone (TPCK) also induced apoptosis in the absence of cycloheximide. On the other hand, the latter two inhibitors decreased cycloheximide-induced apoptosis, assessed either by cell morphologic changes or DNA ladder generation. Benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone and iodoacetamide, inactivators of interleukin 1β-converting enzyme (ICE)-like proteases, did not produce apoptosis and inhibited the induction of apoptosis by cycloheximide, calpain inhibitors, or serine protease inhibitors. These results are consistent with the ICE-like proteases having a central role in proteolysis during apoptosis, while calpain-like proteases and the serine proteases sensitive to DCI or TPCK are not required for generation of the apoptosis phenotype in HL-60 cells.
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- 1996
25. Pharmacokinetic and tissue distribution profile of curculigoside after oral and intravenously injection administration in rats by liquid chromatography–mass spectrometry.
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Yuan, Ting-ting, Xu, Hong-tao, Zhao, Liang, Lv, Lei, He, Yong-jing, Zhang, Nan-dan, Qin, Lu-ping, Han, Ting, and Zhang, Qiao-yan
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ALTERNATIVE medicine , *ANIMAL experimentation , *BIOAVAILABILITY , *BIOPHYSICS , *HISTOLOGICAL techniques , *INTRAVENOUS injections , *LIQUID chromatography , *MASS spectrometry , *RESEARCH methodology , *MEDICINAL plants , *ORAL drug administration , *PHENOLS , *RATS , *PLANT extracts , *DESCRIPTIVE statistics ,RESEARCH evaluation - Abstract
Curculigoside has an extensive pharmacological activity, including estrogen-like, improving sexual behavior, antiosteoporotic, antioxidant, immunomodulatory and neuroprotective effects. However, few investigations have been conducted about the pharmacokinetics and tissue distribution of curculigoside to better understand its behavior and action mechanism in vivo. Thus, a sensitive and reliable liquid chromatography with mass spectrometry (HPLC–MS) method was established and validated for the quantification of curculigoside in rat plasma and tissue samples. Biological samples were processed with methanol precipitation, and naringin was used as the internal standard. Chromatographic separation was performed on an Agilent XDB-C 18 chromatography column (3.0 mm × 50 mm, 1.8 μm) with a mobile phase consisting of acetonitrile and 0.1% formic acid. Quantification was performed by selected ion monitoring with m/z 511.1 [M + HCO 2 ] − for curculigoside and m/z 579.1 [M − H] − for the internal standard. The validated method was successfully applied to the pharmacokinetic and tissue distribution study of curculigoside in rats. Non-compartmental pharmacokinetic parameters indicated that curculigoside had rapid distribution, extensive tissue uptake, and poor absorption into systemic circulation. The values of absolute bioavailability were 0.38%, 0.22% and 0.27% for oral doses of 100, 200 and 400 mg/kg, respectively. The results of the tissue distribution study suggested that curculigoside was distributed into the heart, lung, spleen, intestine, stomach, kidney, thymus, liver, brain, testis, and bone marrow after oral administration of 150 mg/kg. In conclusion, the present study may provide a material basis for study of the pharmacological action of curculigoside, and meaningful insights into further study on clinical application. [ABSTRACT FROM AUTHOR]
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- 2015
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26. Salvia miltiorrhiza: An ancient Chinese herbal medicine as a source for anti-osteoporotic drugs.
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Guo, Yubo, Li, Yu, Xue, Liming, Severino, Richele P., Gao, Sihua, Niu, Jianzhao, Qin, Lu-Ping, Zhang, Dongwei, and Brömme, Dieter
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OSTEOPOROSIS prevention , *ALTERNATIVE medicine , *BIOLOGICAL models , *BIOPHYSICS , *BONE resorption , *BONE growth , *RESEARCH methodology , *MEDICINAL plants , *BOTANIC medicine , *MEDLINE , *ONLINE information services , *PLANT roots , *SYSTEMATIC reviews , *EVIDENCE-based medicine , *PHYTOCHEMICALS , *PLANT extracts , *PROFESSIONAL practice , *TREATMENT duration , *DESCRIPTIVE statistics , *IN vitro studies - Abstract
Ethnopharmacological relevance Red sage ( Salvia miltiorrhiza Bunge), also known as Danshen in Chinese, has been used historically and is currently exploited in combination with other herbs to treat skeletal diseases in traditional Chinese medicine (TCM). With the advance of modern analytical technology, a multitude of bone-targeting, pharmaceutically active, compounds has been isolated and characterized from various sources of TCM including those produced in Salvia miltiorrhiza root. The aim of the review is to provide a comprehensive overview about the historical TCM interpretation of the action of Salvia miltiorrhiza in osteoporosis, its use clinical trials, its main phytochemical constituents, and its action on bone-resorptive and bone formation-stimulating mechanisms in in vitro and in vivo studies. Materials and methods Literature sources used were Pubmed, CNKI.net, Cqvip.com, PubChem, and the Web of Science. For the inquiry, keywords such as Salvia, danshen, osteoporosis, bone, osteoclast and osteoblast were used in various combinations. About 130 research papers and reviews were consulted. Results In TCM, the anti-osteopororotic effect of Salvia miltiorrhiza is ascribed to its action on liver and blood stasis as main therapeutic targets defining osteoporosis. 36 clinical trials were identified which used Salvia miltiorrhiza in combination with other herbs and components to treat post-menopausal, senile, and secondary osteoporosis. On average the trials were characterized by high efficacy (>80%) and low toxicity problems. However, various limitations such as small patient samples, short treatment duration, frequent lack of detailed numerical data, and no clear endpoints must be taken into consideration. To date, more than 100 individual compounds have been isolated from this plant and tested in various animal models and biochemical assays. Compounds display anti-resorptive and bone formation-stimulating features targeting different pathways in the bone remodeling cycle. Pathways affected include the activation of osteoblasts, the modulation of osteoclastogenesis, and the inhibition of collagen degradation by cathepsin K. Conclusions The inclusion of Salvia miltiorrhiza in more than 30% of all herbal clinical trials successfully targeting osteoporosis has stimulated significant interest in the identification and characterization of individual constituents of this herb. The review highlights the anti-osteoporotic potential of Salvia miltiorrhiza in clinical applications and the potential of the herb to provide potent compounds targeting specific pathways in bone resorption and bone formation. [ABSTRACT FROM AUTHOR]
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- 2014
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27. Hepatotoxic constituents and toxicological mechanism of Xanthium strumarium L. fruits.
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Xue, Li-Ming, Zhang, Qiao-Yan, Han, Ping, Jiang, Yi-Ping, Yan, Rong-Di, Wang, Yang, Rahman, Khalid, Jia, Min, Han, Ting, and Qin, Lu-Ping
- Subjects
- *
AMINO acid metabolism , *LIVER analysis , *ALTERNATIVE medicine , *ANIMAL experimentation , *BIOLOGICAL models , *BIOPHYSICS , *CELL physiology , *FATTY acids , *FRUIT , *HEPATOTOXICOLOGY , *HISTOLOGICAL techniques , *LACTATE dehydrogenase , *RESEARCH methodology , *MEDICINAL plants , *MITOCHONDRIA , *MULTIVARIATE analysis , *NUCLEAR magnetic resonance spectroscopy , *RATS , *URINALYSIS , *PHYTOCHEMICALS , *BIOINFORMATICS , *PLANT extracts , *DESCRIPTIVE statistics , *IN vitro studies - Abstract
Abstract: Ethnopharmacological relevance: In the recent years, the international community has attached increasing importance to possible toxicity associated with Traditional Chinese Medicine (TCM). And hepatotoxicity is one of the major concerns, a fundamental pathological process induced by toxicant. This paper is in an attempt to identify the hepatotoxic components in Xanthium strumarium L. fruits (XSF) and interpret the toxicological mechanism induced by XSF. Materials and methods: XSF extract was prepared and seven characteristic components were isolated and identified in XSF water extracts. We evaluated their hepatotoxicity effect on cell proliferation and lactate dehydrogenase (LDH) activity in L-02 and BRL liver cell line. An integrated metabonomics study using high-resolution 1H nuclear magnetic resonance (1H NMR) spectroscopy combined with multivariate statistical analysis was undertake to elucidate the hepatotoxicity mechanism induced in rats by XSF. The urine and serum metabolites were measured after treatment of rats with XSF (7.5, 15.0 and 30.0g/kg/day) for 5 days. Results: The results showed that atractyloside, carboxyatractyloside, 4'-desulphate-atractyloside and XSF induced significant cytotoxic effects in both L-02 and BRL liver cell lines, indicating that atractyloside, carboxyatractyloside, and 4'-desulphate-atractyloside were the toxic components of XSF. When rats were treated with XSF at 30.0g/kg the hepatotoxicity was reflected in the changes observed in serum biochemical profiles and by the histopathological examination of the liver. The levels of VLDL/LDL, 3-HB, lactate, acetate, acetone and glutamate in serum were increased in this group, while d-glucose, choline and valine were decreased. The elevation in the levels of succinate, citrate, 2-oxo-glutamate, glycine, 3-HB, acetate, lactate, hippurate, dimethylglycine, methylamine, dimethylamine, phenylalanine and tryptophan was observed in urine, in contrast a reduction in the intensities of taurine, d-glucose, N-acetyl-glucoprotein and trimethylamine-N-oxide (TMAO) was observed. Conclusions: The results demonstrate that the major hepatotoxicity constituents are atractyloside, carboxyatractyloside and 4'-desulphate-atractyloside, and the hepatotoxicity of XSF involves mitochondrial inability, fatty acid metabolism, and some amino acids metabolism. This integrated 1H NMR -based metabolic profiling approach has been able to capture and probe the metabolic alterations associated with the onset and progression of hepatotoxicity induced by XSF, and permits a comprehensive understanding of systemic toxicity for phytochemicals and other types of xenobiotic agents. [Copyright &y& Elsevier]
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- 2014
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28. Inhibitory effects of the root extract of Litsea cubeba (lour.) pers. on adjuvant arthritis in rats.
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Lin, Bing, Zhang, Hong, Zhao, Xiang-Xiang, Rahman, Khalid, Wang, Ying, Ma, Xue-Qin, Zheng, Cheng-Jian, Zhang, Qiao-Yan, Han, Ting, and Qin, Lu-Ping
- Subjects
- *
RHEUMATOID arthritis , *ENZYME metabolism , *MEDICINAL plants , *ALTERNATIVE medicine , *ANALYSIS of variance , *ANIMAL experimentation , *ANTIRHEUMATIC agents , *BIOPHYSICS , *BODY weight , *DOSE-effect relationship in pharmacology , *DRUG toxicity , *ENZYME-linked immunosorbent assay , *HISTOLOGICAL techniques , *INTERLEUKINS , *RESEARCH methodology , *RATS , *RESEARCH funding , *PLANT roots , *SPLEEN , *THYMUS , *TUMOR necrosis factors , *PLANT extracts , *DATA analysis software , *DESCRIPTIVE statistics , *PHARMACODYNAMICS , *PREVENTION - Abstract
Abstract: Ethnopharmacological relevance: The dried root of Litsea cubeba (Lour.) Pers. (Family Lauraceae) has long been used as a folk remedy in Traditional Chinese Medicine (TCM) and Dai Ethnopharmacy for the treatment of rheumatic diseases in southwestern China. Aim of the study: This study investigated the preventive efficacy of Litsea cubeba root in treating rheumatoid arthritis using Freund's complete adjuvant (CFA) induced arthritis (AA) in rat model. Materials and methods: Arthritis was induced in male Wistar rats by immunization with CFA. Ethanol extract (EELC) and water extract (WELC) of Litsea cubeba root both at 50mg/kg and 200mg/kg were orally administered from a day after the induction of arthritis. Paw swelling, arthritic score, body weight growth rate, index of thymus and spleen were observed, and the production of TNF-α, IL-1β, IL-6 and IL-10 in serum were measured by enzyme-linked immunosorbent assay. The expression levels of inflammatory enzymes like cyclooxygenase and lipoxygenase were also measured by enzyme-linked immunosorbent assay. Moreover, histological changes in the ankle joint were analyzed in AA rats. Results: Both EELC and WELC significantly suppressed paw swelling and arthritic score, increased the loss in body weight and decreased the index of thymus. Histopathological improvement in joint architecture was also observed in EELC, WELC-treated AA rats. The expression levels of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) were decreased on treatment with EELC and WELC. Furthermore, the overproduction of TNF-α, IL-1β and IL-6 were remarkably attenuated in serum of all Litsea cubeba-treated rats, however, IL-10 was markedly increased at doses of 50mg/kg of EELC and WELC. Conclusions: These results indicate that extract of Litsea cubeba root significantly attenuates adjuvant arthritis in rats by decreasing the levels of TNF-α, IL-1β and IL-6 and increasing of IL-10 in serum as well as down-regulate the levels of inflammatory enzymes such as COX-2 and 5-LOX. This suggests that Litsea cubeba root might be used as a therapeutic agent for the treatment of human arthritis. [Copyright &y& Elsevier]
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- 2013
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29. Analysis of the chemical composition, acute toxicity and skin sensitivity of essential oil from rhizomes of Ligusticum chuanxiong
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Zhang, Hong, Han, Ting, Yu, Cheng-Hao, Jiang, Yi-Ping, Peng, Cheng, Ran, Xia, and Qin, Lu-Ping
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MEDICINAL plants , *ALTERNATIVE medicine , *ANIMAL experimentation , *BIOPHYSICS , *CONTACT dermatitis , *DRUG toxicity , *ESSENTIAL oils , *GAS chromatography , *GUINEA pigs , *MASS spectrometry , *RESEARCH methodology , *MICE , *RABBITS , *PHYTOCHEMICALS , *PLANT extracts , *DESCRIPTIVE statistics - Abstract
Abstract: Ethnopharmacological relevance: Ligusticum chuanxiong Hort. (Umbelliferae) is a plant used as medicine and food in China. The essential oil (EO) extracted from its rhizomes possesses many pharmacological activities. However, there have been no scientific reports in the modern literature on the safety of EO. Aims of the study: The objective of this study was to conduct a chemical composition analysis and evaluate acute toxicity and skin sensitivity of EO from rhizomes of Ligusticum chuanxiong. Materials and methods: The chemical composition of hydrodistilled EO was analyzed by gas chromatography-mass spectrometry (GC–MS) and was evaluated in animals for acute toxicity, skin irritation and sensitization tests. Results: Dozens of compounds were detected and the major components of EO were ligustilide and butylidenephthalide with relative contents of 67.46 and 5.06%, respectively. The oral and intra-peritoneal lethal doses of 50% (LD50) in mice were 7.23g/kg (approximately 14,606 times of clinical dose used) and 2.25g/kg (approximately 5091 times of clinical dose used), respectively. The doses of 0.115 and 0.23g/kg EO (approximately 232.5 and 465 times of the respective clinical doses used) revealed slight irritation effects on rabbit skin, but 1g/kg EO (approximately 2020 times of clinical dose used) had no observable effect on guinea pig skin in the skin sensitization test. Conclusions: These experimental results indicate that short term application of EO is probably safe within the range of its clinical doses, but the dose should be controlled for external use due to its slight skin irritation. [Copyright &y& Elsevier]
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- 2012
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30. Sesquiterpenoids and norterpenoids from Vitex negundo
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Zheng, Cheng-Jian, Pu, Jiang, Zhang, Hong, Han, Ting, Rahman, Khalid, and Qin, Lu-Ping
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ALTERNATIVE medicine , *ANALYSIS of variance , *ANTINEOPLASTIC agents , *BIOLOGICAL models , *BIOPHYSICS , *DOSE-effect relationship in pharmacology , *MASS spectrometry , *RESEARCH methodology , *MEDICINAL plants , *NUCLEAR magnetic resonance spectroscopy , *SEEDS , *SPECTRUM analysis , *PLANT extracts , *PHARMACODYNAMICS - Abstract
Abstract: Chemical investigation on the seeds of Vitex negundo has afforded a new furan-containing sesquiterpenoid, negunfurol (1), a new norlabdane-type diterpenoid, negundoal (2), and two new norursane-type triterpenoids, negundonorins A (3) and B (4), together with two know compounds, 3-formyl-4,5-dimethyl-8-oxo-5H-6,7-dihydronaphtho[2,3-b]furan (5) and 3-epi-corosolic acid (6). Their structures and configurations were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. Compound 3 was strongly cytotoxic against ZR-75-30 cell line with IC50 value of 0.56±0.19μg/mL, whereas compound 1 was most active against HL-60 cell line with IC50 value of 0.94±0.26μg/mL. [Copyright &y& Elsevier]
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- 2012
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31. Sesquiterpenoids from Trichoderma atroviride, an endophytic fungus in Cephalotaxus fortunei
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Zheng, Cheng-Jian, Sun, Pei-Xin, Jin, Gui-Lin, and Qin, Lu-Ping
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ALTERNATIVE medicine , *ANALYSIS of variance , *ANIMAL experimentation , *BIOLOGICAL models , *BIOPHYSICS , *PHYSICAL & theoretical chemistry , *DOSE-effect relationship in pharmacology , *FUNGI , *MASS spectrometry , *RESEARCH methodology , *MICE , *NITRIC oxide , *NUCLEAR magnetic resonance spectroscopy - Abstract
Abstract: Two new sesquiterpenoids, identified as (rel 1S, 3R, 4R, 7R)-3-[5-hydroxy-4-methylpent-3-enyl]-1, 3, 7-trimethyl-2-oxabicyclo [2, 2, 1] heptane (1) and (rel 1S, 3R, 4R, 7R)-3-[3, 4-dihydroxy-4-methylpentyl]-1, 3, 7-trimethyl-2-oxabicyclo [2, 2, 1] heptane (2), were isolated from cultures of Trichoderma atroviride (strain no. S361), an endophytic fungal strain residing in the bark of Cephalotaxus fortunei. The structures of compounds 1 and 2 were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. Both compounds 1 and 2 were potent inhibitors on NO production in LPS-stimulated RAW264.7 cells, with IC50 values of 15.3 and 9.1μM, respectively. [Copyright &y& Elsevier]
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- 2011
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32. Analgesic, anti-inflammatory and antipyretic activities of the petroleum ether fraction from the ethanol extract of Desmodium podocarpum
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Zhu, Zhan-Zhou, Ma, Ke-Jia, Ran, Xia, Zhang, Hong, Zheng, Cheng-Jian, Han, Ting, Zhang, Qiao-Yan, and Qin, Lu-Ping
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FEVER , *MEDICINAL plants , *ALTERNATIVE medicine , *ANALGESICS , *ANALYSIS of variance , *ANIMAL experimentation , *ANTI-inflammatory agents , *BIOPHYSICS , *COMPUTER software , *DRUG toxicity , *GAS chromatography , *MASS spectrometry , *MATHEMATICS , *RESEARCH methodology , *MICE , *RATS , *STATISTICS , *T-test (Statistics) , *PLANT extracts , *DATA analysis , *PHARMACODYNAMICS , *PREVENTION - Abstract
Abstract: Ethnopharmacological relevance: Desmodium podocarpum is a plant that has been used in the folk medicine to treat febrile diseases, cough and bleeding wounds. However, there is no scientific basis or reports in the modern literature regarding its effectiveness as an analgesic, anti-inflammatory and antipyretic agent. Aims of the study: The objective of this study is to evaluate the analgesic, anti-inflammatory and antipyretic activities of the petroleum ether fraction (PEF) from the ethanol extract of Desmodium podocarpum. Materials and methods: PEF (50, 100, 200mg/kg) was estimated for its pharmacological properties by using the acetic acid-induced writhing test, the hot plate test, the Carrageenan-induced rat paw edema model, the dimethylbenzene-induced mouse inflammation model, and the lipopolysaccharide (LPS)-induced rat fever model. In addition, the acute toxicity of PEF was also studied. Results: PEF significantly and dose-dependently inhibited the writhing responses in mice, increased reaction time of mice in the hot plate test, reduced carrageenan-induced paw edema in rats and the dimethylbenzene-induced ear edema in mice, and attenuated LPS-induced fever in rats. No death of mice was observed when orally administered PEF up to 4.2g/kg. Conclusions: These findings suggest that PEF possesses evident analgesic, anti-inflammatory and antipyretic activities, and has a favorable safety, which supports the use of Desmodium podocarpum as an analgesic, anti-inflammatory and antipyretic drug in the folk medicine. [Copyright &y& Elsevier]
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- 2011
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33. Bioactivity-guided fractionation for anti-fatigue property of Acanthopanax senticosus
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Huang, Lin-Zhang, Huang, Bao-Kang, Ye, Qi, and Qin, Lu-Ping
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ACANTHOPANAX senticosus , *TREATMENT of psychological stress , *FATIGUE (Physiology) , *BIOACTIVE compounds , *BIOCHEMICAL mechanism of action , *COMPUTERS in botany , *THERAPEUTICS , *FATIGUE prevention , *BLOOD testing , *MEDICINAL plants , *ALTERNATIVE medicine , *ANALYSIS of variance , *ANIMAL experimentation , *ANTHROPOMETRY , *BIOPHYSICS , *COMPUTER software , *KIDNEY function tests , *LACTATE dehydrogenase , *RESEARCH methodology , *MICE , *PLANT roots , *STATISTICS , *PLANT stems , *TRIGLYCERIDES , *PLANT extracts , *DATA analysis ,THERAPEUTIC use of plant extracts - Abstract
Ethnopharmacological relevance: The root of Acanthopanax senticosus (also called Eleutherococcus senticosus or Siberian ginseng) has been used extensively in China, Russia and Japan as an adaptogen to fight against stress and fatigue. Aim of the study: The present study was designed to ascertain the anti-fatigue property of Acanthopanax senticosus by load-weighted swimming test, sleep deprivation test, also to isolate and characterize the active constituents. Materials and methods: Animals were orally administered with the extract of Acanthopanax senticosus. The anti-fatigue effects of the four fractions with different polarities from the 80% ethanol extract, and the different eluates collected from D101 macroporous resin chromatography and eleutheroside E, were examined based on the weight-loaded swimming capacity (physical fatigue) and the change of biochemical parameters in ICR mice. Moreover, the active fraction was later submitted to sleep-deprived mice (mental fatigue). Results: The results shown that the n-butanol fraction significant extends the swimming time of mice to exhaustion. Furthermore, the 60% ethanol–water eluate, more purified eleutherosides (including eleutheroside E, E2 and derivatives), were the exactly active constituents. Two compounds were isolated, which were identified as eleutheroside E, E2. Conclusions: The eleutherosides possess the potent abilities to alleviate fatigue both in physical and mental fatigue. Eleutheroside E may be responsible for the pharmacological effect of anti-fatigue. Furthermore, the possible mechanisms were reduced the level of TG by increasing fat utilization, delayed the accumulation of blood urea nitrogen (BUN), and increased the LDH to reduce the accumulation of lactic acid in muscle and then protect the muscle tissue. [Copyright &y& Elsevier]
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- 2011
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