Home About us Contact
|
Home About us Contact | ||
|
|
||
Lower Cytotoxicity (lower + cytotoxicity)
Selected AbstractsImpaired differentiation and cytotoxicity of natural killer cells in systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 6 2009Yong-Wook Park Objective To determine the cytotoxicity of natural killer (NK) cells and the level of differentiation of hematopoietic stem cells (HSCs) into NK cells in systemic lupus erythematosus (SLE). Methods Patients with SLE (n = 108), rheumatoid arthritis (RA; n = 90), Behçet's disease (n = 39), or ankylosing spondylitis (n = 41) and healthy control subjects (n = 173) were enrolled in the study. NK cell levels, NK cell cytotoxicities, and lymphokine-activated killer (LAK) activities against K562 cells were measured by flow cytometry. Gene expression was assessed by reverse transcription,polymerase chain reaction. NK cells were differentiated from peripheral blood and bone marrow HSCs in vitro. Results Percentages and absolute numbers of NK cells, cytotoxicities, and LAK activities were significantly lower in the peripheral blood of SLE and RA patients than in that of healthy controls. In particular, this NK cell deficiency was more prominent in patients with lupus nephritis and those with thrombocytopenia. Notably, purified NK cells derived from SLE patients, but not RA patients, were found to have lower cytotoxicities and LAK activities than those from healthy controls. This defect of NK cells in SLE patients was found to be related to lower numbers of NK precursors and to the down-regulation of perforin and granzyme in NK cells. The proliferative capacity of HSCs, the percentages of NK cells differentiated from HSCs, and NK cell cytotoxicities were significantly lower in SLE patients. Conclusion In SLE patients, circulating levels of NK cells were diminished and their cytotoxicities were impaired. Furthermore, the differentiation of HSCs into NK cells was found to be defective. These abnormalities possibly contribute to immune system dysregulation in SLE. [source] Functionalization of Chitosan via Atom Transfer Radical Polymerization for Gene DeliveryADVANCED FUNCTIONAL MATERIALS, Issue 18 2010Yuan Ping Abstract It is of crucial importance to modify chitosan-based polysaccharides in the designing of biomedical materials. In this work, atom transfer radical polymerization (ATRP) was employed to functionalize chitosan in a well-controlled manner. A series of new degradable cationic polymers (termed as PDCS) composed of biocompatible chitosan backbones and poly((2-dimethyl amino)ethyl methacrylate) (P(DMAEMA)) side chains of different length were designed as highly efficient gene vectors via ATRP. These vectors, termed as PDCS, exhibited good ability to condense plasmid DNA (pDNA) into nanoparticles with positive charge at nitrogen/phosphorus (N/P) ratios of 4 or higher. All PDCS vectors could well protect the condensed DNA from enzymatic degradation by DNase I and they displayed high level of transfectivity in both COS7, HEK293 and HepG2 cell lines. Most importantly, in comparison with high-molecular-weight P(DMAEMA) and ,gold-standard' PEI (25 kDa), the PDCS vectors showed considerable buffering capacity in the pH range of 7.4 to 5, and were capable of mediating much more efficient gene transfection at low N/P ratios. At their own optimal N/P ratios for trasnsfection, the PDCS/pDNA complexes showed much lower cytotoxicity. All the PDCS vectors were readily to be degradable in the presence of lysozyme at physiological conditions in vitro. These well-defined PDCS polymers have great potentials as efficient gene vectors in future gene therapy. [source] Triton-X-100-modified polymer and microspheres for reversal of multidrug resistanceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2001Zhi Liu Triton X-100 is a non-ionic detergent capable of reversing multidrug resistance (MDR) due to its interaction with cell membranes. However, it interacts with cells in a non-specific way, causing cytotoxicity. This work aimed to develop polymeric chemosensitizers that possess the ability to reverse MDR and lower toxic side effects. When being delivered to tumours, the polymeric chemosensitizers may also have longer retention times in tumours than the free detergent. Triton-X-100-immobilized dextran microspheres (T-MS) and inulin (T-IN) were prepared and characterized. Their cytotoxicity against multidrug-resistant Chinese hamster ovary cells (CHRC5) was compared with that of free Triton X-100 solutions. The in-vitro effect of the products on 3H-vinblastine accumulation by CHRC5 cells was determined. Both T-MS and T-IN showed a marked decrease in the cytotoxicity, as compared with free Triton solutions at equivalent concentrations. Drug accumulation by CHRC5 cells was increased over two fold in the presence of T-MS or T-IN. These results suggest that polymeric drug carriers with MDR-reversing capability and lower cytotoxicity may be prepared by immobilization of chemosensitizers. [source] Lactosylated polyethylenimine for gene transfer into airway epithelial cells: role of the sugar moiety in cell delivery and intracellular trafficking of the complexesTHE JOURNAL OF GENE MEDICINE, Issue 3 2004Stéphanie Grosse Abstract Background As we have previously shown that lactosylated polyethylenimine (PEI) is the most efficient glycosylated PEI for gene transfer into human airway epithelial cells in primary culture, we have studied here the role of the lactose residue in the enhancement of gene transfer efficiency observed with lactosylated PEI as compared with unsubstituted PEI in immortalized (,CFTE29o- cells) and primary human airway epithelial cells. Methods and results After three transfections of 1 h performed daily, 60% of ,CFTE29o- cells were transfected with lactosylated PEI, whereas 25% of cells were transfected with unsubstituted PEI (p < 0.05). Cell viability was 1.8-fold greater with lactosylated PEI as compared with unsubstituted PEI (p < 0.05). As assessed by flow cytometry, the cellular uptake of lactosylated complexes was greater than that of complexes made with unsubstituted PEI (p < 0.05) and involved mostly a receptor-mediated endocytosis. The study of the intracellular trafficking in airway epithelial cells of complexes showed an endosomal and lysosomal accumulation of lactosylated complexes. In the presence of a proton pump inhibitor, the level of lactosylated and unsubstituted PEI-mediated gene expression was reduced more than 20-fold, whereas the cell viability increased to almost 100%. For both complexes, a nuclear localization was observed for less than 5% of intracellular complexes. Conclusions Our results show that the greater gene transfer efficiency observed for lactosylated complexes may be attributed to a higher amount of lactosylated complexes incorporated by airway epithelial cells and a lower cytotoxicity that might be related to reduced endosomolytic properties. However, the lactose residues substituting the PEI did not promote the entry of the plasmid into the nucleus. Copyright © 2004 John Wiley & Sons, Ltd. [source] Biocompatibility and Calcification of Bovine Pericardium Employed for the Construction of Cardiac Bioprostheses Treated With Different Chemical Crosslink MethodsARTIFICIAL ORGANS, Issue 5 2010Eduardo Jorge-Herrero Abstract The use of biological materials in the construction of bioprostheses requires the application of different chemical procedures to improve the durability of the material without producing any undesirable effects. A number of crosslinking methods have been tested in biological tissues composed mainly of collagen. The aim of this study was to evaluate the in vitro biocompatibility, the mechanical properties, and in vivo calcification of chemically modified bovine pericardium using glutaraldehyde acetals (GAAs) in comparison with glutaraldehyde (GA) treatment. Homsy's tests showed that the most cytotoxic treatment is GA whereas GAA treatments showed lower cytotoxicity. Regarding the mechanical properties of the modified materials, no significant differences in stress at rupture were detected among the different treatments. Zeta-Potential showed higher negative values for GA treatment (,4.9 ± 0.6 mV) compared with GAA-0.625% (,2.2 ± 0.5 mV) and GAA-1% (,2.2 ± 0.4 mV), which presented values similar to native tissue. Similar results were obtained for calcium permeability coefficients which showed the highest values for GA treatment (0.12 ± 0.02 mm2/min), being significantly lower for GAA treatments or non-crosslinked pericardium. These results confirmed the higher propensity of the GA-treated tissues for attraction of calcium cations and were in good agreement with the calcification degree obtained after 60 days implantation into young rats, which was significantly higher for the GA group (22.70 ± 20.80 mg/g dry tissue) compared with GAA-0.625% and GAA-1% groups (0.49 ± 0.28 mg/g dry tissue and 3.51 ± 3.27 mg/g dry tissue, respectively; P < 0.001). In conclusion, GAA treatments can be considered a promising alternative to GA treatment. [source] Three-dimensional fibrous PLGA/HAp composite scaffold for BMP-2 deliveryBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2008Hemin Nie Abstract A protein loaded three-dimensional scaffold can be used for protein delivery and bone tissue regeneration. The main objective of this project was to develop recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded poly(D,L -lactide-co-glycolide)/hydroxylapatite (PLGA/HAp) composite fibrous scaffolds through a promising fabrication technique, electrospinning. In vitro release of BMP-2 from these scaffolds, and the attachment ability and viability of marrow derived messenchymal stem cells (MSCs) in the presence of the scaffolds were investigated. The PLGA/HAp composite scaffolds developed in this study exhibit good morphology and it was observed that HAp nanoparticles were homogeneously dispersed inside PLGA matrix within the scaffold. The composite scaffolds allowed sustained (2,8 weeks) release of BMP-2 whose release rate was accelerated with increasing HAp content. It was also shown that BMP-2 protein successfully maintained its integrity and natural conformations after undergoing the process of electrospinning. Cell culture experiments showed that the encapsulation of HAp could enhance cell attachment to scaffolds and lower cytotoxicity. Biotechnol. Bioeng. 2008;99: 223,234. © 2007 Wiley Periodicals, Inc. [source] Total Synthesis of the Cyclodepsipeptide Apratoxin A and Its Analogues and Assessment of Their Biological ActivitiesCHEMISTRY - A EUROPEAN JOURNAL, Issue 29 2006Dawei Ma Prof. Dr. Abstract A novel total synthesis of apratoxin A is described, with key steps including the assembly of its ketide segment through a D -proline-catalyzed direct aldol reaction and Oppolzer's anti aldol reaction and the preparation of its thiazoline unit in a biomimetic synthesis. An oxazoline analogue of apratoxin A has also been elaborated by a similar approach. This compound has a potency against HeLa cell proliferation only slightly lower than that of apratoxin A, whilst a C(40)-demethylated oxazoline analogue of apratoxin A displays a much lower cytotoxicity and the C(37)-epimer and C(37) demethylation product of this new analogue are inactive. These results suggest that the two methyl groups at C(37) and C(40) and the stereochemistry at C(37) are essential for the potent cellular activity of the oxazoline analogue of apratoxin A. Further biological analysis revealed that both synthetic apratoxin A and its oxazoline analogue inhibited cell proliferation by causing cell cycle arrest in the G1 phase. [source] | |||||||||||||