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91.
Purnendu Kumar Sharma Apoorva Panda Adwait Pradhan Jiaxiang Zhang Ruchi Thakkar Chang-Hee Whang Michael A. Repka S. Narasimha Murthy 《AAPS PharmSciTech》2018,19(1):27-35
The transdermal patch formulation has many advantages, including noninvasiveness, an ability to bypass the first-pass metabolism, low dosage requirements, and prolonged drug delivery. However, the instability of solid-state drugs is one of the most critical problems observed in transdermal patch products. Therefore, a well-characterized approach for counteracting stability problems in solid-state drugs is crucial for improving the performance of transdermal patch products. This review provides insight into the solid-state stability of drugs associated with transdermal patch products and offers a comprehensive update on the various approaches being used for improving the stability of the active pharmaceutical ingredients currently being used. 相似文献
92.
Madhura Pradhan Charu Suri Sinjan Choudhary Pradeep Kumar Naik 《Journal of biomolecular structure & dynamics》2018,36(1):195-208
Beta-sitosterol (β-SITO), a phytosterol present in many edible vegetables, has been reported to possess antineoplastic properties and cancer treatment potential. We have shown previously that it binds at a unique site (the ‘SITO-site’) compared to the colchicine binding site at the interface of α- and β-tubulin. In this study, we investigated the anticancer efficacy of β-SITO against invasive breast carcinoma using MCF-7 cells. Since ‘isotypes’ of β-tubulin show tissue-specific expression and many are associated with cancer drug resistance, using computer-assisted docking and atomistic molecular dynamic simulations, we also examined its binding interactions to all known isotypes of β-tubulin in αβ-tubulin dimer. β-SITO inhibited MCF-7 cell viability by up to 50%, compared to vehicle-treated control cells. Indicating its antimetastatic potential, the phytosterol strongly inhibited cell migration. Immunofluorescence imaging of β-SITO-treated MCF-7 cells exhibited disruption of the microtubules and chromosome organization. Far-UV circular dichroism spectra indicated loss of helical stability in tubulin when bound to β-SITO. Docking and MD simulation studies, combined with MM-PBSA and MM-GBSA calculations revealed that β-SITO preferentially binds with specific β-tubulin isotypes (βII and βIII) in the αβ-tubulin dimer. Both these β-tubulin isotypes have been implicated in drug resistance against tubulin-targeted chemotherapeutics. Our data show the tubulin-targeted anticancer potential of β-SITO, and its potential clinical utility against βII and βIII isotype-overexpressing neoplasms. 相似文献
93.
Summary The influence of different depths of submergence (6±1 and 3±1 cm) and moisture tensions (0, 20, 60, 350, 500 and 1000 millibar)
of lateritic sandy loam soil on root porosity and growth parameters of rice, variety IR8 was studied at two different growth
phases under controlled greenhouse conditions. Best rice growth occurred at 3±1 cm submergence and it significantly reduced
with the increase of soil moisture tension. Unlike other growth parameters, root length increased as the soil moisture tension
was raised. The development of pore spaces in rice roots decreased significantly with the increase in soil moisture tension.
However, higher root porosity was observed under greater depths of submergence. Irrespective of soil water condition, the
number and dry weight of the root system showed significant positive correlation with root porosity. Oxygen diffusion rate
in soil, which increased with the increasing moisture tension, was significantly and inversely related with the porosity of
rice root.
Contribution from the Agricultural Engineering Department, Indian Institute of Technology, Kharagpur, West Bengal, India. 相似文献
94.
Madhumita A. Pradhan John A. Blackford Jr. Ballachanda N. Devaiah Petria S. Thompson Carson C. Chow Dinah S. Singer S. Stoney Simons Jr. 《The Journal of biological chemistry》2016,291(1):342-354
Most of the steps in, and many of the factors contributing to, glucocorticoid receptor (GR)-regulated gene induction are currently unknown. A competition assay, based on a validated chemical kinetic model of steroid hormone action, is now used to identify two new factors (BRD4 and negative elongation factor (NELF)-E) and to define their sites and mechanisms of action. BRD4 is a kinase involved in numerous initial steps of gene induction. Consistent with its complicated biochemistry, BRD4 is shown to alter both the maximal activity (Amax) and the steroid concentration required for half-maximal induction (EC50) of GR-mediated gene expression by acting at a minimum of three different kinetically defined steps. The action at two of these steps is dependent on BRD4 concentration, whereas the third step requires the association of BRD4 with P-TEFb. BRD4 is also found to bind to NELF-E, a component of the NELF complex. Unexpectedly, NELF-E modifies GR induction in a manner that is independent of the NELF complex. Several of the kinetically defined steps of BRD4 in this study are proposed to be related to its known biochemical actions. However, novel actions of BRD4 and of NELF-E in GR-controlled gene induction have been uncovered. The model-based competition assay is also unique in being able to order, for the first time, the sites of action of the various reaction components: GR < Cdk9 < BRD4 ≤ induced gene < NELF-E. This ability to order factor actions will assist efforts to reduce the side effects of steroid treatments. 相似文献
95.
T Katsuno T K Pradhan R R Ryan S A Mantey W Hou P J Donohue M A Akeson E R Spindel J F Battey D H Coy R T Jensen 《Biochemistry》1999,38(22):7307-7320
Recently, a fourth member of the bombesin (Bn) receptor family (fBB4-R) was isolated from a cDNA library from the brain of the frog, Bombina orientalis. Its pharmacology and cell biology are largely unknown, and no known natural cell lines or tissues possess sufficient numbers of fBB4-R's to allow either of these to be determined. To address these issues, we have used three different strategies. fBB4-R expression in cells widely used for other Bn receptor subtypes was unsuccessful as was expression in two frog cell lines. However, stable fBB4-R cell lines were obtained in CHO-K1 cells which were shown to faithfully demonstrate the correct pharmacology of the related Bn receptor, the GRP receptor, when expressed in these cells. [DPhe6,betaAla11,Phe13,Nle14]Bn(6-14) was found to have high affinity (Ki = 0.4 nM) for the fBB4 receptor and 125I-[DTyr6,betaala11,Phe13,Nle14]Bn(6-14) to be an excellent ligand for this receptor. The fBB4-R had a unique pharmacology for naturally occurring Bn-related agonists, with the presence of a penultimate phenylalanine being critical for high-affinity interaction. It also had a unique profile for six classes of Bn antagonists. The fBB4-R was coupled to phospholipase C with activation increasing [3H]inositol phosphates and mobilizing Ca2+ almost entirely from cellular sources. There was a close correlation between agonist the receptor occupation and the receptor activation. Three of the five classes of Bn receptor antagonists that interacted with higher affinity with the fBB4-R functioned as fBB4-R antagonists and two as partial agonists. fBB4-R activation stimulated increases in phospholipase D (PLD) over the same range of concentrations at which it activated phospholipase C. These results demonstrate that the fBB4 receptor has a unique pharmacology for agonists and antagonists and is coupled to phospholipase C and D. The availability of these cell lines, this novel ligand, and the identification of three classes of antagonists that can be used as lead compounds should facilitate the further investigation of the pharmacology and cell biology of the BB4 receptor. 相似文献
96.
A Bacolla S Pradhan R J Roberts R D Wells 《The Journal of biological chemistry》1999,274(46):33011-33019
Initial velocity determinations were conducted with human DNA (cytosine-5) methyltransferase (DNMT1) on unmethylated and hemimethylated DNA templates in order to assess the mechanism of the reaction. Initial velocity data with DNA and S-adenosylmethionine (AdoMet) as variable substrates and product inhibition studies with methylated DNA and S-adenosylhomocysteine (AdoHcy) were obtained and evaluated as double-reciprocal plots. These relationships were linear for plasmid DNA, exon-1 from the imprinted small nuclear ribonucleoprotein-associated polypeptide N, (CGG.CCG)(12), (m(5)CGG. CCG)(12), and (CGG.CCG)(73) but were not linear for (CGG. Cm(5)CG)(12). Inhibition by AdoHcy was apparently competitive versus AdoMet and uncompetitive/noncompetitive versus DNA at =20 microM AdoMet. Addition of the product (methylated DNA) to unmethylated plasmid DNA increased V(max(app)) resulting in mixed stimulation and inhibition. Velocity equations indicated a two-step mechanism as follows: first, activation of DNMT1 by methylated DNA that bound to an allosteric site, and second, the addition of AdoMet and DNA to the catalytic site. The preference of DNMT1 for hemimethylated DNA may be the result of positive cooperativity of AdoMet binding mediated by allosteric activation by the methylated CG steps. We propose that this activation plays a role in vivo in the regulation of maintenance methylation. 相似文献
97.
TiD is a standalone application, which relies on basic assumption that a protein must be essential for pathogens survival and non-homologous with host to qualify as putative target. With an input bacterial proteome, TiD removes paralogous proteins, picks essential ones, and excludes proteins homologous with host organisms. The targets illustrate non-homology with at least 40 out of 84 gut microbes, considered safe for human. TiD classifies proposed targets as known, novel and virulent. Users can perform pathway analysis, choke point analysis, interactome analysis, subcellular localization and functional annotations through web servers cross-referenced with the application. Drug targets identified by TiD for Listeria monocytogenes, Bacillus anthracis and Pseudomonas aeruginosa have revealed significant overlaps with previous studies. TiD takes < 2 h to scan putative targets from a bacterial proteome with ~ 5000 proteins; hence, we propose it as a useful tool for rational drug design. TiD is available at http://bmicnip.in/TiD/. 相似文献
98.
99.
Barral DC Cavallari M McCormick PJ Garg S Magee AI Bonifacino JS De Libero G Brenner MB 《Traffic (Copenhagen, Denmark)》2008,9(9):1446-1457
CD1 proteins are a family of major histocompatibility complex (MHC) class I-like antigen-presenting molecules that present lipids to T cells. The cytoplasmic tails (CTs) of all human CD1 isoforms, with the exception of CD1a, contain tyrosine-based sorting motifs, responsible for the internalization of proteins by the clathrin-mediated pathway. The role of the CD1a CT, which does not possess any sorting motifs, as well as its mode of internalization are not known. We investigated the internalization and recycling pathways followed by CD1a and the role of its CT. We found that CD1a can be internalized by a clathrin- and dynamin-independent pathway and that it follows a Rab22a- and ADP ribosylation factor (ARF)6-dependent recycling pathway, similar to other cargo internalized independent of clathrin. We also found that the CD1a CT is S-acylated. However, this posttranslational modification does not determine the rate of internalization or recycling of the protein or its localization to detergent-resistant membrane microdomains (DRMs) where we found CD1a to be enriched. We also show that plasma membrane DRMs are essential for efficient CD1a-mediated antigen presentation. These findings place CD1a closer to MHC class I in its trafficking and potential antigen-loading compartments among CD1 isoforms. Furthermore, we identify CD1a as a new marker for the clathrin- and dynamin-independent and DRM-dependent pathway of internalization as well as the Rab22a- and ARF6-dependent recycling pathway. 相似文献
100.
Basanta Kumar Das Jyotirmayee Pradhan Swagatika Sahu 《Fish & shellfish immunology》2009,26(6):871-876
The study evaluated the effect of dietary doses of Euglena viridis on the immune response and disease resistance of Labeo rohita fingerlings against infection with the bacterial pathogen Aeromonas hydrophila. L. rohita fingerlings were fed with diet containing 0 (Control), 0.1 g, 0.5 g, 1.0 g Euglena powder kg−1 dry diet for 90 days. Biochemical (serum total protein, albumin, globulin, albumin:globulin ratio), haematological (WBC, RBC, haemoglobin content) and immunological (superoxide anion production, lysozyme, serum bactericidal activity) parameters of fish were examined after 30, 60 and 90 days of feeding. Fish were challenged with A. hydrophila 90 days post-feeding and mortalities were recorded over 10 days post-infection. The results demonstrate that fish fed with Euglena showed increased levels of superoxide anion production, lysozyme, serum bactericidal activity, serum protein and albumin (P < 0.05) compared with the control group. Following challenge with A. hydrophila less survivability was observed in the control group (56.65%) than the group fed the experimental diets. The group fed 0.5 g Euglena kg−1 dry diet showed the highest percentage survival (75%). These results indicate that Euglena stimulates the immunity and makes L. rohita more resistant to A. hydrophila infection. 相似文献