排序方式: 共有116条查询结果,搜索用时 15 毫秒
91.
Bashir R Ovais S Yaseen S Hamid H Alam MS Samim M Singh S Javed K 《Bioorganic & medicinal chemistry letters》2011,21(14):4301-4305
Thirteen new 2-pyrazoline derivatives bearing benzenesulfonamide moiety (2a-m) were synthesized by condensing appropriate chalcones with 4-hydrazinonbenzenesulfonamide hydrochloride and tested for anticancer and anti-inflammatory actions. According to the protocol of the National Cancer Institute (NCI) in vitro disease-oriented human cells screening panel assay compounds 2b, 2c, 2e, 2f and 2g exhibited considerable antitumor activities against the entire tested tumor cell lines and showed effective growth inhibition GI50 (MG-MID) values of 2.63, 2.57, 6.61, 3.31 and 2.57 μM, respectively, beside a cyclostatic activity TGI (MG-MID) 9.54, 8.51, 24.0, 19.9 and 8.71 μM, respectively. Two compounds 2g and 2k showed more potent anti-inflammatory activity than celecoxib at 5 h in carrageenan-induced rat paw edema bioassay. These compounds (2g and 2k) proved to have superior gastrointestinal safety profiles as compared to celecoxib, when tested for their ulcerogenic effects. Compounds 2g and 2k showed no inhibition against the enzymatic activity of bovine COX-2 (in vitro). 相似文献
92.
Khurana S Sasono P Fox A Nguyen VK Le QM Pham QT Nguyen TH Nguyen TL Horby P Golding H 《Journal of virology》2011,85(23):12455-12463
Continuing evolution of highly pathogenic (HP) H5N1 influenza viruses in wild birds with transmission to domestic poultry and humans poses a pandemic threat. There is an urgent need for a simple and rapid serological diagnostic assay which can differentiate between antibodies to seasonal and H5N1 strains and that could provide surveillance tools not dependent on virus isolation and nucleic acid technologies. Here we describe the establishment of H5N1 SeroDetect enzyme-linked immunosorbent assay (ELISA) and rapid test assays based on three peptides in HA2 (488-516), PB1-F2 (2-75), and M2e (2-24) that are highly conserved within H5N1 strains. These peptides were identified by antibody repertoire analyses of H5N1 influenza survivors in Vietnam using whole-genome-fragment phage display libraries (GFPDLs). To date, both platforms have demonstrated high levels of sensitivity and specificity in detecting H5N1 infections (clade 1 and clade 2.3.4) in Vietnamese patients as early as 7 days and up to several years postinfection. H5N1 virus-uninfected individuals in Vietnam and the United States, including subjects vaccinated with seasonal influenza vaccines or with confirmed seasonal virus infections, did not react in the H5N1-SeroDetect assays. Moreover, sera from individuals vaccinated with H5N1 subunit vaccine with moderate anti-H5N1 neutralizing antibody titers did not react positively in the H5N1-SeroDetect ELISA or rapid test assays. The simple H5N1-SeroDetect ELISA and rapid tests could provide an important tool for large-scale surveillance for potential exposure to HP H5N1 strains in both humans and birds. 相似文献
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94.
Kopp BT Abdulrahman BA Khweek AA Kumar SB Akhter A Montione R Tazi MF Caution K McCoy K Amer AO 《Biochemical and biophysical research communications》2012,421(2):221-227
Glioblastoma (GBM) is a highly aggressive cancer type characterized by intense neovascularization. Several lines of evidence indicate that blood clotting enzymes play an important role in the tumor microenvironment, mainly through the activation of protease-activated receptors (PAR). In particular, PAR1 and PAR2 isoforms may activate signal transduction pathways that promote a number of pro-tumoral responses. However, little is known concerning the role of PAR1/PAR2 in GBM progression. In this study, we investigated the expression and function of PAR1 and PAR2 in the human GBM cell lines A172 and U87-MG. We also evaluated the effect of agonist peptides for PAR1 (PAR1-AP) and PAR2 (PAR2-AP) on signaling pathways and the expression of vascular endothelial growth factor (VEGF). Immunoblotting assays showed that A172 and U87-MG constitutively express PAR1 and PAR2. Treatment of GBM cells with PAR1-AP or PAR2-AP enhanced Akt (protein kinase B) and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in a time-dependent manner. LY29042 and PD98059, inhibitors of the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways, decreased PAR-mediated activation of Akt and ERK1/2, respectively. In addition, we observed that PAR2, but not PAR1, activation increased VEGF secretion in U87-MG and A172 cells. Notably, only PD98059 reduced PAR2-mediated VEGF production by GBM cells. Our results suggest that PAR2 modulates VEGF production through the MAPK/ERK1/2 pathway, and not the PI3K/Akt pathway, in human GBM cell lines. Therefore, the PAR2/MAPK signaling axis might be regarded as a relevant target for adjuvant treatment of GBM with a possible impact on tumor angiogenesis. 相似文献
95.
Vijay Anand Shalini Jaswal Surender Singh Sudarshan Kumar Manoj Kumar Jena Arvind Kumar Verma Munna Lal Yadav Jagadeesh Janjanam Masoud Lotfan Dhruba Malakar Ajay Kumar Dang Tushar Kumar Mohanty Jai Kumar Kaushik Ashok Kumar Mohanty 《Apoptosis : an international journal on programmed cell death》2016,21(2):209-224
96.
Chakrabhavi Dhananjaya Mohan V. Srinivasa Shobith Rangappa Lewis Mervin Surender Mohan Shardul Paricharak Sefer Baday Feng Li Muthu K. Shanmugam Arunachalam Chinnathambi M. E. Zayed Sulaiman Ali Alharbi Andreas Bender Gautam Sethi Basappa Kanchugarakoppal S. Rangappa 《PloS one》2016,11(4)
Overactivation of PI3K/Akt/mTOR is linked with carcinogenesis and serves a potential molecular therapeutic target in treatment of various cancers. Herein, we report the synthesis of trisubstituted-imidazoles and identified 2-chloro-3-(4, 5-diphenyl-1H-imidazol-2-yl) pyridine (CIP) as lead cytotoxic agent. Naïve Base classifier model of in silico target prediction revealed that CIP targets RAC-beta serine/threonine-protein kinase which comprises the Akt. Furthermore, CIP downregulated the phosphorylation of Akt, PDK and mTOR proteins and decreased expression of cyclin D1, Bcl-2, survivin, VEGF, procaspase-3 and increased cleavage of PARP. In addition, CIP significantly downregulated the CXCL12 induced motility of breast cancer cells and molecular docking calculations revealed that all compounds bind to Akt2 kinase with high docking scores compared to the library of previously reported Akt2 inhibitors. In summary, we report the synthesis and biological evaluation of imidazoles that induce apoptosis in breast cancer cells by negatively regulating PI3K/Akt/mTOR signaling pathway. 相似文献
97.
Sagare Deepti B. Shetti Prashant Surender M. Reddy S. S. 《Molecular breeding : new strategies in plant improvement》2019,39(2):1-20
Molecular Breeding - Molecular breeding is capable of improving important agricultural crop traits by controlling functional genes, aiming to attain high yield, stability and quality. During this... 相似文献
98.
Shamik Polley Sachinandan De Subhasis Batabyal Ramakant Kaushik Paras Yadav Jaspreet Singh Arora Saibal Chattopadhyay Subhransu Pan Biswajit Brahma Tirtha Kumar Datta Surender Lal Goswami 《Small Ruminant Research》2009,85(2-3):122-129
The Black Bengal is a prolific goat breed in India. Natural mutations in prolific sheep breeds have shown that the transforming growth factor beta (TGF-β) super family ligands such as growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and their type I receptor (bone morphogenetic protein receptor, BMPR1B) are crucial for ovulation and as well as for increasing litter size. Mutations in any of these genes increased prolificacy in sheep. Based on the known mutation information in sheep PCR primers were designed to screen known polymorphism in 88 random Black Bengal goats. Only the BMPR1B gene was polymorphic. Three genotypes of animals were detected in tested animals with mutant (FecBB) and wild type (FecB+) alleles were 0.57 and 0.43, respectively. Non-carrier, heterozygous carrier and homozygous carrier Black Bengal does had 2.7, 3.04 and 3.11 kids, respectively. All known point mutations of BMP15 and GDF9 genes were monomorphic in the animals tested. These results preliminarily showed that the BMPR1B gene might be a major gene that influences prolificacy of Black Bengal goats. 相似文献
99.
Fillon S Soulis K Rajasekaran S Benedict-Hamilton H Radin JN Orihuela CJ El Kasmi KC Murti G Kaushal D Gaber MW Weber JR Murray PJ Tuomanen EI 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(9):6182-6191
The current model of innate immune recognition of Gram-positive bacteria suggests that the bacterial cell wall interacts with host recognition proteins such as TLRs and Nod proteins. We describe an additional recognition system mediated by the platelet-activating factor receptor (PAFr) and directed to the pathogen-associated molecular pattern phosphorylcholine that results in the uptake of bacterial components into host cells. Intravascular choline-containing cell walls bound to endothelial cells and caused rapid lethality in wild-type, Tlr2(-/-), and Nod2(-/-) mice but not in Pafr(-/-) mice. The cell wall exited the vasculature into the heart and brain, accumulating within endothelial cells, cardiomyocytes, and neurons in a PAFr-dependent way. Physiological consequences of the cell wall/PAFr interaction were cell specific, being noninflammatory in endothelial cells and neurons but causing a rapid loss of cardiomyocyte contractility that contributed to death. Thus, PAFr shepherds phosphorylcholine-containing bacterial components such as the cell wall into host cells from where the response ranges from quiescence to severe pathophysiology. 相似文献
100.
Kumar S Khanduja KL Verma N Verma SC Avti PK Pathak CM 《Molecular and cellular biochemistry》2008,307(1-2):109-119
We investigated the in vitro efficacy of all-trans retinoic acid (ATRA) and alpha-tocopherol succinate (α-TS) alone and in combination on the induction of cell death in freshly
isolated leukemic cells obtained from chronic myeloid leukemia (CML) patients. In vitro cytotoxicity and induction of lipid
peroxidation by ATRA (10 μM) and α-TS (25 or 50 μM) were evaluated in primary leukemic cells by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide] assay and malondialdehyde formation respectively. Treatment of leukemic cells with α-TS alone or in combination with
ATRA significantly (P < 0.05) decreased the cell viability in a concentration and time dependent manner as compared to peripheral blood mononuclear
cells obtained from normal healthy controls. Lipid peroxidation was enhanced by 98% (P < 0.05) on combined treatment of cells with ATRA (10 μM) and α-TS (50 μM). ATRA alone did not enhance the externalization
of phosphatidyl serine as studied by annexin-V binding using fluorescence activated cell sorter analysis, whereas in combination
with α-TS it increased to 400% at 12 h. The treatment of leukemic cells to combination of ATRA with α-TS significantly decreased
(P < 0.05) mitochondrial membrane potential and enhanced lysosomal destabilization. The combination of these drugs also increased
mitochondrial and cytosolic reactive oxygen species (ROS) production, nitric oxide levels, and caspase-3 activity significantly
and caused DNA fragmentation at 24 h in a concentration dependent manner in the leukemic cells. Our data suggest that ATRA
in combination with α-TS efficiently induces apoptosis in leukemic cells, which may be a useful therapeutic modality in CML
patients. 相似文献