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991.
Arivusudar Marimuthu Sandip Chavan Gajanan Sathe Nandini A. Sahasrabuddhe Srinivas M. Srikanth Santosh Renuse Sartaj Ahmad Aneesha Radhakrishnan Mustafa A. Barbhuiya Rekha V. Kumar H.C. Harsha David Sidransky Joseph Califano Akhilesh Pandey Aditi Chatterjee 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(11):2308-2316
Protein biomarker discovery for early detection of head and neck squamous cell carcinoma (HNSCC) is a crucial unmet need to improve patient outcomes. Mass spectrometry-based proteomics has emerged as a promising tool for identification of biomarkers in different cancer types. Proteins secreted from cancer cells can serve as potential biomarkers for early diagnosis. In the current study, we have used isobaric tag for relative and absolute quantitation (iTRAQ) labeling methodology coupled with high resolution mass spectrometry to identify and quantitate secreted proteins from a panel of head and neck carcinoma cell lines. In all, we identified 2,472 proteins, of which 225 proteins were secreted at higher or lower abundance in HNSCC-derived cell lines. Of these, 148 were present in higher abundance and 77 were present in lower abundance in the cancer-cell derived secretome. We detected a higher abundance of some previously known markers for HNSCC including insulin like growth factor binding protein 3, IGFBP3 (11-fold) and opioid growth factor receptor, OGFR (10-fold) demonstrating the validity of our approach. We also identified several novel secreted proteins in HNSCC including olfactomedin-4, OLFM4 (12-fold) and hepatocyte growth factor activator, HGFA (5-fold). IHC-based validation was conducted in HNSCC using tissue microarrays which revealed overexpression of IGFBP3 and OLFM4 in 70% and 75% of the tested cases, respectively. Our study illustrates quantitative proteomics of secretome as a robust approach for identification of potential HNSCC biomarkers. This article is part of a Special Issue entitled: An Updated Secretome. 相似文献
992.
The objective of this study is to formulate lyophilized oral sustained release polymeric nanoparticles of nateglinide in order to decrease dosing frequency, minimize side effects, and increase bioavailability. Nateglinide-loaded poly Ɛ-caprolactone nanoparticles were prepared by emulsion solvent evaporation with ultrasonication technique and subjected to various studies for characterization including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, photon correlation spectroscopy and evaluated for in vitro drug release and pharmacodynamic studies. The influence of increase in polymer concentration, ultrasonication time, and solvent evaporation rate on nanoparticle properties was investigated. The formulations were optimized based on the above characterization, and the formulation using 5% polymer, 3-min sonication time, and rota-evaporated was found to have the best drug entrapment efficiency of 64.09 ± 4.27% and size of 310.40 ± 11.42 nm. Based on SEM, nanoparticles were found to be spherical with a smooth surface. In vitro drug release data showed that nanoparticles sustained the nateglinide release for over 12 h compared to conventional tablets (Glinate 60 mg), and drug release was found to follow Fickian mechanism. In vivo studies showed that nanoparticles prolonged the antidiabetic activity of nateglinide in rats significantly (p ≤ 0.05) compared to the conventional tablets (Glinate 60 mg) over a period of 12 h. Accelerated stability data indicated that there was minimal to no change in drug entrapment efficiency.KEY WORDS: drug encapsulation efficiency, nanoparticles, poly Ɛ-caprolactone (PCL), probe sonication 相似文献
993.
A fruity aroma-producing strain WG4 was isolated from a water sample collected from the Western Ghats, India. The 16S rRNA
gene sequence analysis of strain WG4 indicated that Chryseobacterium indologenes, a member of the family ‘Flavobacteriaceae’ is the closest related species with a pair-wise sequence similarity of 98.6%.
Strain WG4 produces a fruity aroma when grown on nutrient or trypticase soy agar plates. The fruity aroma is more when the
strain WG4 is grown on agar plates compared to their growth in broth. The aromatic compounds produced by the strain WG4 were
identified as ester compounds and were confirmed as ethyl-2-methylbutyrate and ethyl-3-methylbutyrate based on Gas Chromatography–Mass
Spectrometry (GC–MS) analysis and using standard reference compounds. Even after repeated subcultures strain WG4 produced
the same aroma in high intensity. Thus, strain WG4 could serve as a source for the production of these flavour compounds. 相似文献
994.
Laxminarayan S Tadmor G Diamond SG Miller E Franceschini MA Brooks DH 《Biological cybernetics》2011,105(5-6):371-397
Habituation is a generic property of the neural response to repeated stimuli. Its strength often increases as inter-stimuli relaxation periods decrease. We propose a simple, broadly applicable control structure that enables a neural mass model of the evoked EEG response to exhibit habituated behavior. A key motivation for this investigation is the ongoing effort to develop model-based reconstruction of multi-modal functional neuroimaging data. The control structure proposed here is illustrated and validated in the context of a biophysical neural mass model, developed by Riera et?al. (Hum Brain Mapp 27(11):896-914, 2006; 28(4):335-354, 2007), and of simplifications thereof, using data from rat EEG response to medial nerve stimuli presented at frequencies from 1 to 8?Hz. Performance was tested by predictions of both the response to the next stimulus based on the current one, and also of continued stimuli trains over 4-s time intervals based on the first stimulus in the interval, with similar success statistics. These tests demonstrate the ability of simple generative models to capture key features of the evoked response, including habituation. 相似文献
995.
This study investigated physiological and behavioral functions of a novel gene identified from the termite Reticulitermes flavipes. The gene, named deviate, encodes an apparent ligand binding protein from the takeout-homologous family. Initial studies were conducted to investigate deviate mRNA expression among termite castes and body regions, and changes in response to light-dark conditions, starvation, temperature, and juvenile hormone (JH). Deviate has ubiquitous caste and tissue expression, including antennal expression. Consistent with characteristics of other takeout family members, deviate expression is responsive to photophase conditions (p<0.1), and feeding, temperature, and JH (p<0.05). Using RNA-interference (RNAi) techniques, short-interfering RNAs (siRNAs) homologous to the deviate gene were synthesized and injected into worker termites, which were then subjected to bioassays designed to (1) induce caste differentiation or (2) measure various behavioral aspects of foraging and trail following. No impacts on JH-dependent caste differentiation were observable. However, trail following accuracy was significantly reduced in termites that received deviate siRNA injections, and this pattern generally mirrored deviate mRNA attenuation and recovery after RNAi. In a subsequent distance foraging bioassay, deviate-silenced termites exhibited equal feeding levels to controls, suggesting the deviate gene is not linked to general vigor or the ability/motivation of termites to move and forage. These findings are among the first linking the expression of a termite gene with eusocial behavior; they illustrate the connection between deviate expression and trailing behavior, which is a key evolutionary adaptation vital to subterranean social insects such as termites and ants. 相似文献
996.
Prabhu S Srinivas V Ramakrishna T Raman B Rao ChM 《Free radical biology & medicine》2011,51(3):755-762
Oxidative stress, Cu2+ homeostasis, and small heat shock proteins (sHsp's) have important implications in several neurodegenerative diseases. The ubiquitous sHsp αB-crystallin is an oligomeric protein that binds Cu2+. We have investigated the relative contributions of the N- and C-terminal (C-TDαB-crystallin) domains of αB-crystallin to its Cu2+-binding and redox-attenuation properties and mapped the Cu2+-binding regions. C-TDαB-crystallin binds Cu2+ with slightly less affinity and inhibits Cu2+-catalyzed, ascorbate-mediated generation of ROS to a lesser extent than αB-crystallin. [Cu2+]/[subunit] stoichiometries for redox attenuation by αB-crystallin and C-TDαB-crystallin are 5 and 2, respectively. Both αB-crystallin and C-TDαB-crystallin also inhibit the Fenton reaction of hydroxyl radical formation. Trypsinization of αB-crystallin bound to a Cu2+-NTA column and MALDI-TOF analysis of column-bound peptides yielded three peptides located in the N-terminal domain, and in-solution trypsinization of αB-crystallin followed by Cu2+-NTA column chromatography identified four additional Cu2+-binding peptides located in the C-terminal domain. Thus, Cu2+-binding regions are distributed in the N- and C-terminal domains. Small-angle X-ray scattering and sedimentation-velocity measurements indicate quaternary structural changes in αB-crystallin upon Cu2+ binding. Our study indicates that an oligomer of αB-crystallin can sequester a large number (~ 150) of Cu2+ ions. It acts like a “Cu2+ sponge,” exhibits redox attenuation of Cu2+, and has potential roles in Cu2+ homeostasis and in preventing oxidative stress. 相似文献
997.
998.
999.
Sasmal PK Reddy DS Talwar R Venkatesham B Balasubrahmanyam D Kannan M Srinivas P Kumar KS Devi BN Jadhav VP Khan SK Mohan P Chaudhury H Bhuniya D Iqbal J Chakrabarti R 《Bioorganic & medicinal chemistry letters》2011,21(1):562-568
The synthesis and biological evaluation of novel pyrazole-3-carboxamide derivatives as CB1 antagonists are described. As a part of eastern amide SAR, various chemically diverse motifs were introduced. In general, a range of modifications were well tolerated. Several molecules with high polar surface area were also identified as potent CB1 receptor antagonists. The in vivo proof of principle for weight loss is exemplified with a lead compound from this series. 相似文献
1000.
Kantevari S Addla D Bagul PK Sridhar B Banerjee SK 《Bioorganic & medicinal chemistry》2011,19(16):4772-4781
A series of novel 2-butyl-4-chloro-1-methylimidazole embedded aryl and heteroaryl derived chalcones and pyrazoles were synthesized and evaluated for their angiotensin converting enzyme (ACE) inhibitory activity. The condensation of 2-butyl-4-chloro-1-methylimidazole-5-carboxaldehyde with various aryl and heteroaryl methyl ketones in the presence of 10% aqueous NaOH in methanol proceeded efficiently to give the respective chalcones in very good yields. Further, the reaction of chalcones with hydrazine hydrate in acetic acid gave substituted pyrazole analogues. Screening all 36 new compounds using ACE inhibition assay, resulted chalcones with better ACE inhibitory activity compared to the respective pyrazole analogues. Among the chalcones 4a-r, three compounds, (E)-3-(2-butyl-4-chloro-1-methyl-1H-imidazol-5-yl)-1-(5-chlorothiophen-2-yl)prop-2-enone 4i, (E)-3-(2-butyl-4-chloro-1-methyl-1H-imidazol-5-yl)-1-(1H-pyrrol-2-yl)prop-2-enone 4l, (E)-3-(2-butyl-4-chloro-1-methyl-1H-imidazol-5-yl)-1-(dibenzo[b,d] thiophen-2-yl)prop-2-enone 4q were resulted as most active ACE inhibitors with IC(50) of 3.60 μM, 2.24 μM, and 2.68 μM, respectively. 相似文献