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51.
In vitro testing for genotoxicity of violacein assessed by Comet and Micronucleus assays 总被引:2,自引:0,他引:2
Andrighetti-Fröhner CR Kratz JM Antonio RV Creczynski-Pasa TB Barardi CR Simões CM 《Mutation research》2006,603(1):97-103
Chromobacterium violaceum is a Gram (-) bacteria found in water samples and soils from tropical and subtropical regions of the world. Violacein, the major pigment produced by these bacteria, has been shown to have antibiotic, antitumoral and trypanocidal activities. In the present work, the genotoxicity of violacein was investigated in four different cell lines by using the alkaline Comet assay and in VERO cells using the Micronucleus test. In the alkaline Comet assay, violacein, when tested at concentrations ranging from 0.19 to 1.5 microM, did not induce a significant increase in DNA damage in HEp-2 and MA104 cells. However, violacein was positive for DNA damage in FRhK-4 cells and for both DNA damage and micronuclei in VERO cells, in a concentration-response relationship. The results of this study indicated that violacein is genotoxic in VERO and FRhK-4 cells. These findings contribute to a comprehensive evaluation of the pharmacological potential of violacein. 相似文献
52.
Ryppa C Mann-Steinberg H Fichtner I Weber H Satchi-Fainaro R Biniossek ML Kratz F 《Bioconjugate chemistry》2008,19(7):1414-1422
Integrins, especially integrin alpha vbeta3, are attractive receptors for vascular targeting strategies. Recently, a divalent RGD peptidomimetic, E-[c(RGDfK)2], has been described that demonstrates increased uptake in human ovarian carcinoma OVCAR-3 xenograft tumors. Inspired by these results, we set out to develop doxorubicin conjugates with E-[c(RGDfK)2] by binding two different maleimide derivatives of doxorubicin to E-[c(RGDfK)2] that was thiolated with iminothiolane. In this way, two water-soluble derivatives were obtained, E-[c(RGDfK)2]-DOXO-1 and E-[c(RGDfK)2]-DOXO-2. In E-[c(RGDfK)2]-DOXO-1, doxorubicin was bound to the peptide through a stable amide bond, and in E-[c(RGDfK)2]-DOXO-2, a MMP-2/MMP-9 cleavable octapeptide was introduced between doxorubicin and the peptide. The rationale for a MMP-2/MMP-9-cleavable linker was that MMP-2 and MMP-9 bind to integrin alpha vbeta3 and both are overexpressed in tumor vasculature. In addition, analogous control doxorubicin-containing peptides bearing c(RADfK) that does not bind to integrin alpha vbeta3 were synthesized, i.e., c(RADfK)-DOXO-1 and c(RADfK)-DOXO-2. Whereas E-[c(RGDfK) 2]-DOXO-2 was cleaved effectively by MMP-2 and in OVCAR-3 tumor homogenates releasing a doxorubicin-tetrapeptide or doxorubicin as the final cleavage product, no release of doxorubicin was observed for E-[c(RGDfK)2]-DOXO-1. Proliferation of HUVEC in the presence of MMP-2-cleavable doxorubicin-containing peptides exhibited 6- to 10-fold increased inhibition compared to the amide-linked doxorubicin-containing peptides. In addition, inhibition of HUVEC sprouting during a 24 h exposure was approximately 3-fold stronger for E-[c(RGDfK) 2]-DOXO-2 and 20-fold stronger for the reference peptide conjugate c(RADfK)-DOXO-2 than for doxorubicin alone. In vivo studies in an OVCAR-3 xenograft model demonstrated no or only moderate antitumor efficacy for either E-[c(RGDfK)2], E-[c(RGDfK)2]-DOXO-1, E-[c(RGDfK)2]-DOXO-2, or c(RADfK)-DOXO-2, even at doses of 3 x 24 mg/kg doxorubicin equivalents, compared to an improved antitumor effect for doxorubicin at 2 x 8 mg/kg. 相似文献
53.
Marcilio CP de Souto Ivan G Costa Daniel SA de Araujo Teresa B Ludermir Alexander Schliep 《BMC bioinformatics》2008,9(1):497
Background
The use of clustering methods for the discovery of cancer subtypes has drawn a great deal of attention in the scientific community. While bioinformaticians have proposed new clustering methods that take advantage of characteristics of the gene expression data, the medical community has a preference for using "classic" clustering methods. There have been no studies thus far performing a large-scale evaluation of different clustering methods in this context. 相似文献54.
Kratz JM Andrighetti-Fröhner CR Kolling DJ Leal PC Cirne-Santos CC Yunes RA Nunes RJ Trybala E Bergström T Frugulhetti IC Barardi CR Simões CM 《Memórias do Instituto Oswaldo Cruz》2008,103(5):437-442
The synthetic n-alkyl esters of gallic acid (GA), also known as gallates, especially propyl, octyl and dodecyl gallates, are widely employed as antioxidants by food and pharmaceutical industries. The inhibitory effects of GA and 15 gallates on Herpes Simplex Virus type 1 (HSV-1) and Human Immunodeficiency Virus (HIV-1) replication were investigated here. After a preliminary screening of these compounds, GA and pentyl gallate (PG) seemed to be the most active compounds against HSV-1 replication and their mode of action was characterized through a set of assays, which attempted to localize the step of the viral multiplication cycle where impairment occurred. The detected anti-HSV-1 activity was mediated by the inhibition of virus attachment to and penetration into cells, and by virucidal properties. Furthermore, an anti-HIV-1 activity was also found, to different degrees. In summary, our results suggest that both compounds could be regarded as promising candidates for the development of topical anti-HSV-1 agents, and further studies concerning the anti-HIV-1 activity of this group of molecules are merited. 相似文献
55.
Balen Manuela Gomes Gabriela Rotta Kratz Jadel M. Simões Cláudia M. O. Valério Alexsandra de Oliveira Débora 《Bioprocess and biosystems engineering》2017,40(2):265-270
Bioprocess and Biosystems Engineering - Antioxidants are substances that defend cells against damage, kidnapping and destroying free radicals. They have been largely used in the food industry due... 相似文献
56.
F Kratz J Drevs G Bing C Stockmar K Scheuermann P Lazar C Unger 《Bioorganic & medicinal chemistry letters》2001,11(15):2001-2006
Two doxorubicin albumin conjugates (A-DP1 and A-DP2), which differ in their substrate specificity for the matrix metalloproteinases MMP2 and MMP9, were prepared by binding maleimide doxorubicin peptide derivatives to the cysteine-34 position of human serum albumin. The incorporated octapeptide, Gly-Pro-Gln-Arg-Ile-Ala-Gly-Gln, in A-DP2 is not cleaved by activated MMP2 and MMP9 in contrast to Gly-Pro-Leu-Gly-Ile-Ala-Gly-Gln incorporated in A-DP1 that is cleaved efficiently by activated MMP2 and MMP9 liberating a doxorubicin tetrapeptide. A-DP1 showed antiproliferative activity in a murine renal cell carcinoma line in the low micromolar range (IC(50) value approximately 0.2 microM). 相似文献
57.
McRae S Chen X Kratz K Samanta D Henchey E Schneider S Emrick T 《Biomacromolecules》2012,13(7):2099-2109
Novel pentafluorophenyl (PFP)-ester-functionalized phosphorylcholine (PC) polymers of different architectures were prepared and conjugated to lysozyme as a model protein. Linear and two-arm poly(2-methacryloyloxyethyl phosphorylcholine) (polyMPC) structures containing PFP functionality at the chain-end were prepared by atom transfer radical polymerization (ATRP) from novel initiators. Additional conjugates were prepared from phosphorylcholine-substituted cyclooctene (PC-COE) polymers containing PFP-ester bearing comonomers. The polymer-protein conjugates were characterized by HPLC, FPLC, and DLS and were seen to retain most (~80% or greater) of their native enzymatic activity. Pharmacokinetic profiles of the polymer-protein conjugates were studied in mice and found to increase the circulation half-life compared with lysozyme alone. 相似文献
58.
Data “publication” seeks to appropriate the prestige of authorship in the peer-reviewed literature to reward researchers who create useful and well-documented datasets. The scholarly communication community has embraced data publication as an incentive to document and share data. But, numerous new and ongoing experiments in implementation have not yet resolved what a data publication should be, when data should be peer-reviewed, or how data peer review should work. While researchers have been surveyed extensively regarding data management and sharing, their perceptions and expectations of data publication are largely unknown. To bring this important yet neglected perspective into the conversation, we surveyed ∼ 250 researchers across the sciences and social sciences– asking what expectations“data publication” raises and what features would be useful to evaluate the trustworthiness, evaluate the impact, and enhance the prestige of a data publication. We found that researcher expectations of data publication center on availability, generally through an open database or repository. Few respondents expected published data to be peer-reviewed, but peer-reviewed data enjoyed much greater trust and prestige. The importance of adequate metadata was acknowledged, in that almost all respondents expected data peer review to include evaluation of the data’s documentation. Formal citation in the reference list was affirmed by most respondents as the proper way to credit dataset creators. Citation count was viewed as the most useful measure of impact, but download count was seen as nearly as valuable. These results offer practical guidance for data publishers seeking to meet researcher expectations and enhance the value of published data. 相似文献
59.
The possibility to use a suspended tridimensional matrix as scaffolding for re-epithelialization of in vitro cutaneous wounds was investigated with the aid of a human in vitro wound healing model based on viable full thickness skin. Macroporous gelatin microcarriers, CultiSpher-S, were applied to in vitro wounds and cultured for 21 days. Tissue sections showed incorporation of wound edge keratinocytes into the microcarriers and thicker neoepidermis in wounds treated with microcarriers. Thickness of the neoepidermis was measured digitally, using immunohistochemical staining of keratins as epithelial demarcation. Air-lifting of wounds enhanced stratification in control wounds as well as wounds with CultiSpher-S. Immunohistochemical staining revealed expression of keratin 5, keratin 10, and laminin 5 in the neoepidermal component. We conclude that the CultiSpher-S microcarriers can function as tissue guiding scaffold for re-epithelialization of cutaneous wounds. 相似文献
60.
Effects of an invertebrate grazer on the spatial arrangement of a benthic microhabitat 总被引:1,自引:1,他引:0
We demonstrated the effect of an aquatic herbivore on the spatial arrangement of benthic algal biomass within artificial stream channels. Transects of ceramic tiles were exposed to a gradient of snail (Physella) densities in a 30 d experiment. We observed positive effects of snails on the mean abundance of overstory algae (the filamentous chlorophyte Cladophora and associated epiphytes), an important benthic microhabitat in streams. Snails altered several aspects of the spatial arrangement of overstory algae. Snails reduced the strength of downstream gradients in overstory biomass, as well as residual variability around these gradients. Geostatistical analysis revealed that snails also reduced the strength of spatial dependence, and so reduced spatial heterogeneity of the overstory, at small scales (<40 cm). As a result, organisms inhabiting the overstory might experience a more fragmented habitat landscape at high snail densities. In addition, snails increased the scale of spatial dependence in understory algal biomass (algae remaining on tiles after overstory was removed) from 10 cm to 40 cm. Consumer effects on the spatial arrangement of a microhabitat argue for the inclusion of feedbacks between the biota and the environment in spatially-explicit models. 相似文献