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排序方式: 共有1336条查询结果,搜索用时 10 毫秒
971.
Francesco Caruso Claudio Pettinari Fabio Marchetti Miriam Rossi Cristian Opazo Sarvesh Kumar Sakshi Balwani Balaram Ghosh 《Bioorganic & medicinal chemistry》2009,17(17):6166-6172
Recent reports show that the natural β-diketone curcumin displays important biological properties regarding the intercellular adhesion molecule-1 (ICAM-1), which plays a critical role in the immune responses and inflammation. In this study the ICAM-1 inhibitory activity of β-diketone compounds, which are curcumin models lacking aromatic peripheral hydroxyl and methoxy groups, along with some metal derivatives is investigated. β-Diketones are systematically more active than metal complexes and the best obtained inhibition is 75% for both groups. The best inhibitors are 4-benzoyl-3-methyl-1-phenyl-pyrazol-5-one (HQPh) among the ligands, and sodium benzoylacetonato among metal derivatives. These results appear in line with the reported antitumor activity of related species. Since 4-acyl-5-pyrazolones posses four tautomeric forms, those corresponding to HQPh were investigated using density functional theory. Docking of all HQPh tautomers on ICAM-1 protein was performed suggesting one keto-enol form favored to act in biological environment. 相似文献
972.
Immunohistochemical study of human pterygium 总被引:2,自引:0,他引:2
The purpose of this study has been to evaluate the immunohistochemical characteristics of human pterygial tissues in order to ascertain the possible contribution of an immunological mechanism in the pathogenesis of pterygium and to investigate the presence in the pterygial tissues of some melanoma-associated antigens, in order to evaluate if there may be a small possibility of correlation of the two diseases. Human biopsy specimens of pterygium were obtained by surgery for pterygium excision. Tissue segments were fixed and processed for paraffin embedding. Microtome sections were treated for the immunohistochemical demonstration of IgA, IgM, IgG, CD3, CD20, CD68, HLA-DR, Protein S100, HMB45, and Melan A using the avidin-biotin peroxidase method or the streptavidin biotin-alkaline phosphatase method. The findings suggest that all the effector components of the mucosal immune system are present in the human pterygium and, among the most sensitive markers for melanoma, only S100 shows immunoreactivity. An immunopathogenetic mechanism seems to be responsible for the pathogenesis of pterygium, perhaps being caused by pre-existing conjunctivitis or microtrauma in combination with the patient's predisposition. No correlation between pterygium and melanoma was found. 相似文献
973.
Bremer S Pellizzer C Adler S Paparella M de Lange J 《Alternatives to laboratory animals : ATLA》2002,30(Z2):107-109
The importance of developing in vitro tests for embryotoxicity is discussed, and ECVAM's work with its collaborators is summarised. Studies are in progress to find new endpoints for use in the scientifically validated embryonic stem (ES) cell test, so that the potential for chemical effects on endodermal, mesodermal and/or ectodermal differentiation can be identified. This involves, inter alia, the use of genetically modified ES cells. 相似文献
974.
Ibarra C Estrada M Carrasco L Chiong M Liberona JL Cardenas C Díaz-Araya G Jaimovich E Lavandero S 《The Journal of biological chemistry》2004,279(9):7554-7565
In the heart, insulin-like growth factor-1 (IGF-1) is a pro-hypertrophic and anti-apoptotic peptide. In cultured rat cardiomyocytes, IGF-1 induced a fast and transient increase in Ca(2+)(i) levels apparent both in the nucleus and cytosol, releasing this ion from intracellular stores through an inositol 1,4,5-trisphosphate (IP(3))-dependent signaling pathway. Intracellular IP(3) levels increased after IGF-1 stimulation in both the presence and absence of extracellular Ca(2+). A different spatial distribution of IP(3) receptor isoforms in cardiomyocytes was found. Ryanodine did not prevent the IGF-1-induced increase of Ca(2+)(i) levels but inhibited the basal and spontaneous Ca(2+)(i) oscillations observed when cardiac myocytes were incubated in Ca(2+)-containing resting media. Spatial analysis of fluorescence images of IGF-1-stimulated cardiomyocytes incubated in Ca(2+)-containing resting media showed an early increase in Ca(2+)(i), initially localized in the nucleus. Calcium imaging suggested that part of the Ca(2+) released by stimulation with IGF-1 was initially contained in the perinuclear region. The IGF-1-induced increase on Ca(2+)(i) levels was prevented by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, thapsigargin, xestospongin C, 2-aminoethoxy diphenyl borate, U-73122, pertussis toxin, and betaARKct (a peptide inhibitor of Gbetagamma signaling). Pertussis toxin also prevented the IGF-1-dependent IP(3) mass increase. Genistein treatment largely decreased the IGF-1-induced changes in both Ca(2+)(i) and IP(3). LY29402 (but not PD98059) also prevented the IGF-1-dependent Ca(2+)(i) increase. Both pertussis toxin and U73122 prevented the IGF-1-dependent induction of both ERKs and protein kinase B. We conclude that IGF-1 increases Ca(2+)(i) levels in cultured cardiac myocytes through a Gbetagamma subunit of a pertussis toxin-sensitive G protein-PI3K-phospholipase C signaling pathway that involves participation of IP(3). 相似文献
975.
Detection of tissue-specific effects by methotrexate on differentiating mouse embryonic stem cells 总被引:2,自引:0,他引:2
Pellizzer C Bello E Adler S Hartung T Bremer S 《Birth defects research. Part B, Developmental and reproductive toxicology》2004,71(5):331-341
BACKGROUND: Pluripotent embryonic stem (ES) cells offer a unique possibility to monitor the differentiation of several cell types in vitro. This study attempts to identify marker genes during in vitro cell differentiation of murine ES cells and allow a prediction of chemical effects on cell differentiation of specific target tissues. The study focused on the expression pattern of key genes involved in cardiomyocyte and osteoblast differentiation: Oct-4, Brachyury, Nkx2.5, alpha myosin heavy chain, Cbfa1, and Osteocalcin. METHODS: Methotrexate was selected due to its well-characterized teratogenic effects. Several in vivo studies have demonstrated the specific interactions of methotrexate with bone formation whereas the cardiovascular system is not specifically affected after exposure to low concentration. The capability of murine ES cells to differentiate in vitro into cardiomyocytes as well as into osteoblasts have been used to demonstrate the target cell specificity in vitro, at non-cytotoxic concentration. RESULTS: Exposure of differentiating ES cells did not result in any gene profile modification of the selected cardiomyocyte specific genes, whereas the expression of osteoblast specific key genes, Cbfa1 and Osteocalcin, decreased. At the latter stages of skeletal differentiation we observed a 30% decrease in gene expression for Cbfa1 and a 60% decrease for Osteocalcin, with reference to the control. Early marker genes for undifferentiated cells and mesodermal cells were not modified after methotrexate treatment. CONCLUSIONS: These results show the possibility to integrate specific in vitro tests for teratogenicity in a test strategy for developmental toxicity. 相似文献
976.
Relationship between total superoxide dismutase activity with lipid peroxidation, dynamics and morphological parameters in canine semen 总被引:2,自引:0,他引:2
There is a lack of information regarding biochemical studies on canine semen. The knowledge of canine sperm metabolism is important because this species has differences in fertility among males, but biochemical studies are not well developed in this species. Reactive oxygen species (ROS) are active molecules produced during the oxygen reduction that have been implicated in several deleterious effects on the function and viability of spermatozoa when they are produced at high concentrations. Peroxidation of the plasma membrane phospholipids leads to a loss of motility, viability, and cytosolic elements, metabolic changes and structural alterations in spermatozoa. The most important antioxidant enzyme involved in ROS detoxification in mammalian spermatozoa is superoxide dismutase (SOD). The aims of the present study were to determine the presence of SOD-like activity in different fractions of canine semen, and to determine the relationship between SOD-like activity and different morphological, dynamical and biochemical parameters in canine spermatozoa. We demonstrated the presence of SOD-like activity in canine seminal plasma and spermatozoa; the negative correlation between SOD-like activity and lipid peroxidation concentrations in spermatozoa suggests a protective effect of this enzymatic activity against the potential oxidative stress in canine spermatozoa. A significant negative correlation between percentage of abnormal spermatozoa, and the percentage of progressive motility or vigor was found. Abnormal spermatozoa not only showed a deformed shape, moreover there was an energetic motility system failure. The presence of SOD-like activity in seminal plasma, spermatic, and postspermatic fractions of canine semen was demonstrated for the first time. 相似文献
977.
978.
Oprea TI Bologa CG Edwards BS Prossnitz ER Sklar LA 《Journal of biomolecular screening》2005,10(5):419-426
An empirical scheme to evaluate and prioritize screening hits from high-throughput screening (HTS) is proposed. Negative scores are given when chemotypes found in the HTS hits are present in annotated databases such as MDDR and WOMBAT or for testing positive in toxicity-related experiments reported in TOXNET. Positive scores were given for higher measured biological activities, for testing negative in toxicity-related literature, and for good overlap when profiled against drug-related properties. Particular emphasis is placed on estimating aqueous solubility to prioritize in vivo experiments. This empirical scheme is given as an illustration to assist the decision-making process in selecting chemotypes and individual compounds for further experimentation, when confronted with multiple hits from high-throughput experiments. The decision-making process is discussed for a set of G-protein coupled receptor antagonists and validated on a literature example for dihydrofolate reductase inhibition. 相似文献
979.
Subtropical soil microbial isolates were screened for carbohydrate, tributyrin, or olive oil hydrolysis using agar plates supplemented with the corresponding substrates. A heterotrophic, aerobic, Gram-positive strain displaying activity on tributyrin was selected and further characterized. Analysis of the morphological and physiological traits of the strain placed it as a member of the genus Rhodococcus. Further 16S rDNA sequencing revealed a 99% identity to Rhodococcus erythropolis. The strain displayed lipolytic activity on fatty-acid-derivative substrates of short chain length, with cell extract fractions having highest activity, as confirmed by the presence, after zymogram analysis, of a ca. 60-kDa intracellular protein band with activity on 4-methylumbelliferone-butyrate substrate. The presence of such a lipolytic enzyme, similar to those found in other Gram-positive bacteria, indicates that the strain could be of interest for certain biotechnological applications, like the synthesis of pharmaceuticals or biocide detoxification. 相似文献
980.
Rapid recrystallization of cyclomaltooctaose (gamma-cyclodextrin, gamma-CD) from aqueous solution resulted in formation of a columnar structure with only water as the guest molecule. Upon vacuum drying at 90 degrees C for 15 h, gamma-CD, which was initially in the columnar structure, became amorphous. Complementary water vapor sorption and wide-angle X-ray diffractometry experiments were performed on columnar gamma-CD in its vacuum dried and as-precipitated states to elucidate its stability in humid environments and the crystal structure present at varying sorption levels. These experiments show that both types of gamma-CD transform to the cage crystal structure upon exposure to water vapor at 40 degrees C and with an activity of 1.0. Sorption equilibrium is reached long before the crystal structure transformation is complete, indicating that a significant amount of molecular mobility exists in the various hydrated gamma-CD crystal structures. 相似文献