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101.
Harish Chandra Pal Samriti Sharma Leah Ray Strickland Jyoti Agarwal Mohammad Athar Craig A. Elmets Farrukh Afaq 《PloS one》2013,8(10)
Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2) have emerged as two effective clinical targets for non-small-cell lung cancer (NSCLC). In the present study, we found that delphinidin, an anthocyanidin, present in pigmented fruits and vegetables, is a potent inhibitor of both EGFR and VEGFR2 in NSCLC cells that overexpress EGFR/VEGFR2. Using these cells, we next determined the effects of delphinidin on cell growth and apoptosis in vitro and on tumor growth and angiogenesis in vivo. Delphinidin (5-60 µM) treatment of NSCLC cells inhibited the activation of PI3K, and phosphorylation of AKT and MAPKs. Additionally, treatment of NSCLC cells with delphinidin resulted in inhibition of cell growth without having significant toxic effects on normal human bronchial epithelial cells. Specifically, treatment of NCI-H441 and SK-MES-1 cells with delphindin (5-60 µM) resulted in (i) cleavage of PARP protein, (ii) activation of caspase-3 and -9, (iii) downregulation of anti-apoptotic proteins (Bcl2, Bcl-xL and Mcl-1), (iv) upregulation of pro-apoptotic proteins (Bax and Bak), and (v) decreased expression of PCNA and cyclin D1. Furthermore, in athymic nude mice subcutaneously implanted with human NSCLC cells, delphinidin treatment caused a (i) significant inhibition of tumor growth, (ii) decrease in the expression of markers for cell proliferation (Ki67 and PCNA) and angiogenesis (CD31 and VEGF), and (iii) induction of apoptosis, when compared with control mice. Based on these observations, we suggest that delphinidin, alone or as an adjuvant to current therapies, could be used for the management of NSCLC, especially those that overexpress EGFR and VEGFR2. 相似文献
102.
Many attempts on optimization of sorghum [Sorghum bicolor (L.)
Moench] tissue culture induction media have been made, but the culture system
remains with some bottlenecks compared to that of other crops. This study aimed
at assessing the suitability of various induction media to produce embryogenic
callus (yellow and friable) with high induction rates and reduced phenolic
exudation. The six culture medium modifications: 3 based on Murashige and
Skoog (MS) medium and one each based on Chu N6, Gamborg B5 and 190-2
media respectively were applied in the culture of mature embryos from 10
sorghum genotypes. Although there was a genotype influence on the attainment
of a yellow callus, friability of the callus was determined to be dependent on the
culture medium and not the genotype. Half strength MS medium with 0.2 mg/l
2,4-D with 2.8 g/l Gelrite® as the gelling agent modified with 1.0 g/l KH2PO4,
1.0 g/l L-proline, 1.0 g/l L-asparagine and 0.16 mg/l CuSO4·5H2O (type E) was
found to be the most effective resulting in about 60% yellow coloured callus
induction with 25% friability. Addition of CuSO4·5H2O, KH2PO4, L-proline and
L-asparagine significantly reduced the phenolic production. Half strength MS
medium was observed to contribute to quality callus production when compared
to full strength MS media modified with the compounds. The half strength MS
medium was also observed to suppress phenolic production. Medium 190-2
produced the highest regeneration frequency (40%) among the 3-regeneration
media tested. The results provide information on a suitable sorghum callus
induction medium necessary for embryogenesis. 相似文献
103.
Sharma Himanshu Bhandawat Abhishek Rahim Mohammed Saba Kumar Pankaj Choudhoury Mohini Pal Roy Joy 《Molecular biology reports》2020,47(5):3485-3500
Molecular Biology Reports - Introns experience lesser selection pressure, thus are liable for higher polymorphism. Intron Length Polymorphic (ILP) markers designed from exon-flanking introns... 相似文献
104.
The Nest is a concave-shaped structural motif in proteins formed by consecutive enantiomeric left-handed (L) and right-handed (R) helical conformation of the backbone. This important motif subsumes many turn and helix capping structures and binds electron-rich ligands. Simple Nests are either RL or LR. Larger Nests (>2 residues long) may be RLR, LRL, RLRL, and so forth, being considered as composed of overlapping simple Nests. The larger Nests remain under-explored despite their widely known contributions to protein function. In our study, we address whether the recurrence of enantiomeric geometry in the larger Nests constrains the peptide backbone such that distinct compositional and conformational preferences are seen compared to simple Nests. Our analysis reveals the critical role of the L helical torsion angle in the formation of larger Nests. This can be observed through the higher propensity of residue or secondary structure combinations in LR and LRL backbone conformation in comparison to RL or RLR, although LR/LRL is considerably lower by occurrence. We also find that the most abundant doublets and triplets in Nests have a propensity for particular secondary structures, suggesting a strong sequence-structure relationship in the larger Nest. Overall, our analysis corroborates distinct features of simple and the larger Nests. Such insights would be helpful towards in-vitro design of peptides and peptidomimetic studies. 相似文献
105.
Anutthaman Parthasarathy Jörg Kahnt Nilanjan Pal Chowdhury Wolfgang Buckel 《Archives of microbiology》2013,195(12):781-797
Evidence is presented for a pathway of phenylalanine catabolism in the hyperthermophilic archaeon Archaeoglobus fulgidus involving the following enzymes—phenylalanine:2-oxoglutarate aminotransferase, phenyllactate dehydrogenase, radical iron–sulphur 3-phenyllactyl-CoA dehydratase, phenylpropionyl-CoA dehydrogenase, aryl pyruvate ferredoxin oxidoreductase, ADP-forming acetyl-CoA synthetase and family III CoA-transferase. Hitherto amino acid degradation pathways involving radical iron–sulphur dehydratases have been characterised only in mesophilic clostridia and related bacteria. The difference here is that the pathway is not fermentative but coupled to sulphate reduction. Initial experiments also show the utilisation of tryptophan as a growth substrate and the decarboxylation of caffeate by cell extracts, suggesting the potential to catabolise different classes of aromatic compounds. 相似文献
106.
ABSTRACT:?The demand for natural and nonpersistent insecticides is increasing day by day. Plant cell cultures could be an alternative to conventional methods of production of insecticides from field-grown plants. In vitro cultured plant cells produce a wide array of insecticides as a part of their secondary metabolism. Their ability to synthesize key enzymes and the manipulation of these could lead to the enhanced production of many insecticides of industrial importance. The development of a high-yielding hairy root culture system for thiophenes, nicotine, and phytoecdysones is of considerable interest. In this article, the current literature on various factors that influence the growth, production, and secretion of six insecticidal compounds, namely, pyrethrins, azadirachtin, thiophenes, nicotine, rotenoids, and phytoecdysones which have been prospects for the scale-up of cell cultures, genetic engineering to obtain transgenic plants, and metabolically engineered plants for increased production of bio-molecules, has been discussed. Environmental safety clearance and the future prospects of application of bio-molecules for plant-derived insecticides are presented. 相似文献
107.
Abstract A complete three dimensional model for the LexA repressor dimer bound to the recA operator site consistent with relevant biochemical and biophysical data for the repressor was proposed from our laboratory when no crystal structure of LexA was available. Subsequently, the crystal structures of four LexA mutants Δ1–67 S119A, S119A, G85D and Δ1-67 quadruple mutant in the absence of operator were reported. It is examined in this paper to what extent our previous model was correct and how, using the crystal structure of the operator-free LexA dimer we can predict an improved model of LexA dimer bound to recA operator. In our improved model, the C-domain dimerization observed repeatedly in the mutant operator-free crystals is retained but the relative orientation between the two domains within a LexA molecule changes. The crystal structure of wild type LexA with or without the recA operator cannot be solved as it autocleaves itself. We argue that the ‘cleavable’ cleavage site region found in the crystal structures is actually the more relevant form of the region in wildtype LexA since it agrees with the value of the pre-exponential Arrhenius factor for its auto- cleavage, absence of various types of trans-cleavages, difficulty in modifying the catalytic serine by diisopropyl flourophosphate and lack of cleavage at Arg 81 by trypsin; hence the concept of a ‘conformational switch’ inferred from the crystal structures is meaningless. 相似文献
108.
Adrian K. K. Teo Rebecca Windmueller Bente B. Johansson Ercument Dirice Pal R. Njolstad Erling Tjora Helge Raeder Rohit N. Kulkarni 《The Journal of biological chemistry》2013,288(8):5353-5356
Maturity onset diabetes of the young (MODY) is an autosomal dominant disease. Despite extensive research, the mechanism by which a mutant MODY gene results in monogenic diabetes is not yet clear due to the inaccessibility of patient samples. Induced pluripotency and directed differentiation toward the pancreatic lineage are now viable and attractive methods to uncover the molecular mechanisms underlying MODY. Here we report, for the first time, the derivation of human induced pluripotent stem cells (hiPSCs) from patients with five types of MODY: MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), MODY5 (HNF1B), and MODY8 (CEL) with a polycistronic lentiviral vector expressing a Cre-excisable human “stem cell cassette” containing the four reprogramming factors OCT4, KLF4, SOX2, and CMYC. These MODY-hiPSCs morphologically resemble human pluripotent stem cells (hPSCs), express pluripotency markers OCT4, SOX2, NANOG, SSEA-4, and TRA-1–60, give rise to derivatives of the three germ layers in a teratoma assay, and are karyotypically normal. Overall, our MODY-hiPSCs serve as invaluable tools to dissect the role of MODY genes in the development of pancreas and islet cells and to evaluate their significance in regulating beta cell function. This knowledge will aid future attempts aimed at deriving functional mature beta cells from hPSCs. 相似文献
109.
Gheorghe Benga 《European biophysics journal : EBJ》2013,42(1):33-46
NMR measurements of the diffusional permeability of the human adult red blood cell (RBC) membrane to water (P d) and of the activation energy (E a,d) of the process furnished values of P d ~ 4 × 10?3 cm/s at 25 °C and ~6.1 × 10?3 cm/s at 37 °C, and E a,d ~ 26 kJ/mol. Comparative NMR measurements for other species showed: (1) monotremes (echidna and platypus), chicken, little penguin, and saltwater crocodile have the lowest P d values; (2) sheep, cow, and elephant have P d values lower than human P d values; (3) cat, horse, alpaca, and camel have P d values close to those of humans; (4) guinea pig, dog, dingo, agile wallaby, red-necked wallaby, Eastern grey kangaroo, and red kangaroo have P d values higher than those of humans; (5) mouse, rat, rabbit, and “small and medium size” marsupials have the highest values of P d (>8.0 × 10?3 cm/s at 25 °C and >10.0 × 10?3 cm/s at 37 °C). There are peculiarities of E a,d values for the RBCs from different species. The maximum inhibition of diffusional permeability of RBCs induced by incubation with p-chloromercuribenzene sulfonate varied between 0 % (for the chicken and little penguin) to ~50 % (for human, mouse, cat, sheep, horse, camel, and Indian elephant), and ~60–75 % (for rat, guinea pig, rabbit, dog, alpaca, and all marsupials). These results indicate that no water channel proteins (WCPs) or aquaporins are present in the membrane of RBCs from monotremes (echidna, platypus), chicken, little penguin and saltwater crocodile whereas WCPs from the membranes of RBCs from marsupials have peculiarities. 相似文献
110.