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31.
The relative release in vitro of endothelin‐1, zinc‐α2‐glycoprotein (ZAG), lipocalin‐2, CD14, RANTES (regulated on activation, normal T cell expressed and secreted protein), lipoprotein lipase (LPL), osteoprotegerin (OPG), fatty acid–binding protein 4 (FABP‐4), visfatin/PBEF/Nampt, glutathione peroxidase‐3 (GPX‐3), intracellular cell adhesion molecule 1 (ICAM‐1), and amyloid A was examined using explants of human adipose tissue as well as the nonfat cell fractions and adipocytes from obese women. Over a 48‐h incubation the majority of the release of LPL was by fat cells whereas that of lipocalin‐2, RANTES, and ICAM‐1 was by the nonfat cells present in human adipose tissue. In contrast appreciable amounts of OPG, amyloid A, ZAG, FABP‐4, GPX‐3, CD14, and visfatin/PBEF/Nampt were released by both fat cells and nonfat cells. There was an excellent correlation (r = 0.75) between the ratios of adipokine release by fat cells to nonfat cells over 48 h and the ratio of their mRNAs in fat cells to nonfat cells at the start of the incubation. The total release of ZAG, OPG, RANTES, and amyloid A by incubated adipose tissue explants from women with a fat mass of 65 kg was not different from that by women with a fat mass of 29 kg. In contrast that of ICAM‐1, FABP‐4, GPX‐3, visfatin/PBEF/Nampt, CD14, lipocalin‐2, LP, and endothelin‐1 was significantly greater in tissue from women with a total fat mass of 65 kg.  相似文献   
32.
Targeted drug delivery systems for cancer improves anti-tumor efficacy and reduces systemic toxicity by restricting availability of cytotoxic drugs within tumors. Targeting moieties, such as natural ligands (folic acid, transferrin, and biotin) which are overexpressed on tumors, have been used to enhance liposome-encapsulated drug accumulation within tumors and resulted in better control. In this report, we explored the scope of targeting ligand folic acid, which is incorporated in liposome systems using folic acid-modified cholesterol (CPF), enabled highly selective tumor-targeted delivery of liposome-encapsulated doxorubicin and resulted in increased cytotoxicity within tumors. Folate-tagged poloxamer-coated liposomes (FDL) were found to have significantly higher cellular uptake than conventional poloxamer-coated liposomes (DL), as confirmed by fluorometric analysis in B16F10 melanoma cells. Biodistribution study of the radiolabeled liposomal system indicated the significantly higher tumor uptake of FDL as compared to DL. Anti-tumor activity of FDL against murine B16F10 melanoma tumor-bearing mice revealed that FDL inhibited tumor growth more efficiently than the DL. Taken together, the results demonstrated the significant potential of the folate-conjugated nanoliposomal system for drug delivery to tumors.  相似文献   
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The mechanism by which a disordered peptide nucleates and forms amyloid is incompletely understood. A central domain of β‐amyloid (Aβ21–30) has been proposed to have intrinsic structural propensities that guide the limited formation of structure in the process of fibrillization. In order to test this hypothesis, we examine several internal fragments of Aβ, and variants of these either cyclized or with an N‐terminal Cys. While Aβ21–30 and variants were always monomeric and unstructured (circular dichroism (CD) and nuclear magnetic resonance spectroscopy (NMRS)), we found that the addition of flanking hydrophobic residues in Aβ16–34 led to formation of typical amyloid fibrils. NMR showed no long‐range nuclear overhauser effect (nOes) in Aβ21–30, Aβ16–34, or their variants, however. Serial 1H‐15N‐heteronuclear single quantum coherence spectroscopy, 1H‐1H nuclear overhauser effect spectroscopy, and 1H‐1H total correlational spectroscopy spectra were used to follow aggregation of Aβ16–34 and Cys‐Aβ16–34 at a site‐specific level. The addition of an N‐terminal Cys residue (in Cys‐Aβ16–34) increased the rate of fibrillization which was attributable to disulfide bond formation. We propose a scheme comparing the aggregation pathways for Aβ16–34 and Cys‐Aβ16–34, according to which Cys‐Aβ16–34 dimerizes, which accelerates fibril formation. In this context, cysteine residues form a focal point that guides fibrillization, a role which, in native peptides, can be assumed by heterogeneous nucleators of aggregation.  相似文献   
36.
This paper studies the peristaltic transport of a viscoelastic fluid (with the fractional second-grade model) through an inclined cylindrical tube. The wall of the tube is modelled as a sinusoidal wave. The flow analysis is presented under the assumptions of long wave length and low Reynolds number. Caputo's definition of fractional derivative is used to formulate the fractional differentiation. Analytical solutions are developed for the normalized momentum equations. Expressions are also derived for the pressure, frictional force, and the relationship between the flow rate and pressure gradient. Mathematica numerical computations are then performed. The results are plotted and analysed for different values of fractional parameter, material constant, inclination angle, Reynolds number, Froude number and peristaltic wave amplitude. It is found that fractional parameter and Froude number resist the flow pattern while material constant, Reynolds number, inclination of angle and amplitude aid the peristaltic flow. Furthermore, frictional force and pressure demonstrate the opposite behaviour under the influence of the relevant parameters emerging in the equations of motion. The study has applications in uretral biophysics, and also potential use in peristaltic pumping of petroleum viscoelastic bio-surfactants in chemical engineering and astronautical applications involving conveyance of non-Newtonian fluids (e.g. lubricants) against gravity and in conduits with deformable walls.  相似文献   
37.
Backbone dynamics and conformational properties of drug peptide salmon calcitonin have been studied in aqueous solution using nuclear magnetic resonance (NMR). Although salmon calcitonin (sCT) is largely unfolded in solution (as has been reported in several circular dichroism studies), the secondary Hα chemical shifts and three bond HN–Hα coupling constants indicated that most of the residues of the peptide are populating the α‐helical region of the Ramachandran (?, ψ) map. Further, the peptide in solution has been found to exhibit multiple conformational states exchanging slowly on the NMR timescale (102–103 s?1), inferred by the multiple chemical shift assignments in the region Leu4–Leu12 and around Pro23 (for residues Gln20–Tyr22 and Arg24). Possibly, these slowly exchanging multiple conformational states might inhibit symmetric self‐association of the peptide and, in part, may account for its reduced aggregation propensity compared with human calcitonin (which lacks this property). The 15N NMR‐relaxation data revealed (i) the presence of slow (microsecond‐to‐millisecond) timescale dynamics in the N‐terminal region (Cys1–Ser5) and core residues His17 and Asn26 and (ii) the presence of high frequency (nanosecond‐to‐picosecond) motions in the C‐terminal arm. Put together, the various results suggested that (i) the flexible C‐terminal of sCT (from Thr25–Thr31) is involved in identification of specific target receptors, (ii) whereas the N‐terminal of sCT (from Cys1–Gln20) in solution – exhibiting significant amount of conformational plasticity and strong bias towards biologically active α‐helical structure – facilitates favorable conformational adaptations while interacting with the intermembrane domains of these target receptors. Thus, we believe that the structural and dynamics features of sCT presented here will be useful guiding attributes for the rational design of biologically active sCT analogs. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.  相似文献   
38.
A series of azatricyclodiones and octahydro-benzo[f]isoindoles have been synthesized by (4+2) Diels-Alder cycloaddition of maleimides with furfuryl amine. Reaction of azatricyclodiones with isocyanates led to the respective ureides. All of the compounds were screened against a number of bacteria and fungi. One of the compounds (2) displayed moderate antitubercular activity while two compounds (2) and (4) inhibited the fungal growth at 25 μg/mL.  相似文献   
39.
Glutathione-S-transferase(s) (E.C.2.5.1.18, GSTs) have been investigated in parasitic protozoans with respect to their biochemistry and they have been identified as potential vaccine candidates in protozoan parasites and as a target in the synthesis of new antiparasitic agents. In a search towards the identification of novel biochemical targets for antimalarial drug design, the area of Plasmodium glutathione metabolism provides a number of promising chemotherapeutic targets. GST activity was determined in various subcellular fractions of malarial parasites Plasmodium yoelii and was found to be localized mainly in the cytosolic fraction (specific activity, c. 0.058 ± 0.016 μmol/min/mg protein). Hemin, a known inhibitor of mammalian GST(s), maximally inhibited this enzyme from P. yoelii to nearly 86%. In a search towards synthetic modulators of malarial GST(s), 575 compounds belonging to various chemical classes were screened for their effect on crude GST from P. yoelii and 92 compounds belonging to various chemical classes were studied on recombinant GST from P. falciparum. Among all the compounds screened, 83 compounds inhibited/stimulated the enzyme from P. yoelii/P. falciparum to the extent of 40% or more.  相似文献   
40.
Localized surface plasmon resonance incurred by silver nanoparticles is used to enhance the photoelectric conversion efficiency of a TiO2 nanorod-based dye-sensitized solar cell (DSSC). Improved light transmission is observed experimentally in silver nanoparticle-coated FTO glass. The transmission data are used to explore the effect on electrical parameters of DSSC using theoretical model. Current density increased from 11.7 to 12.34 mA/cm2 and open-circuit voltage increased from 704 to 709.5 mV. Overall efficiency enhancement of 6.67 % is observed in TiO2 nanorod-based DSSC due to plasmon-induced light trapping.  相似文献   
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