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91.
92.
Halesha D. Basavarajappa Bit Lee Xiang Fei Daesung Lim Breedge Callaghan Julie A. Mund Jamie Case Gangaraju Rajashekhar Seung-Yong Seo Timothy W. Corson 《PloS one》2014,9(4)
Preventing pathological ocular angiogenesis is key to treating retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. At present there is no small molecule drug on the market to target this process and hence there is a pressing need for developing novel small molecules that can replace or complement the present surgical and biologic therapies for these neovascular eye diseases. Previously, an antiangiogenic homoisoflavanone was isolated from the bulb of a medicinal orchid, Cremastra appendiculata. In this study, we present the synthesis of a novel homoisoflavanone isomer of this compound. Our compound, SH-11052, has antiproliferative activity against human umbilical vein endothelial cells, and also against more ocular disease-relevant human retinal microvascular endothelial cells (HRECs). Tube formation and cell cycle progression of HRECs were inhibited by SH-11052, but the compound did not induce apoptosis at effective concentrations. SH-11052 also decreased TNF-α induced p38 MAPK phosphorylation in these cells. Intriguingly, SH-11052 blocked TNF-α induced IκB-α degradation, and therefore decreased NF-κB nuclear translocation. It decreased the expression of NF-κB target genes and the pro-angiogenic or pro-inflammatory markers VCAM-1, CCL2, IL8, and PTGS2. In addition SH-11052 inhibited VEGF induced activation of Akt but not VEGF receptor autophosphorylation. Based on these results we propose that SH-11052 inhibits inflammation induced angiogenesis by blocking both TNF-α and VEGF mediated pathways, two major pathways involved in pathological angiogenesis. Synthesis of this novel homoisoflavanone opens the door to structure-activity relationship studies of this class of compound and further evaluation of its mechanism and potential to complement existing antiangiogenic drugs. 相似文献
93.
94.
95.
Distribution of amiloride-sensitive sodium channels in the oral cavity of the hamster 总被引:3,自引:3,他引:0
The distribution of amiloride-sensitive sodium channels (ASSCs) in taste
buds isolated from the oral cavity of hamsters was assessed by patch clamp
recording. In contrast to the case for rats, taste cells from the
fungiform, foliate and vallate papillae and from the soft palate all
contain functional ASSCs. The differential distribution of ASSCs between
the hamster and the rat may be important for understanding the physiology
underlying the differing behavioral responses of these species to sodium
salts.
相似文献
96.
Physical properties of biological membranes determined by the fluorescence of the calcium ionophore A23187 总被引:5,自引:0,他引:5
Interactions between the divalent cation ionophore, A23187, and the divalent cations Ca2+, Mg2+, and Mn2+ were studied in sarcoplasmic reticulum and mitochondria. Conductance measurements suggest that A23187 facilitates the movement of divalent cations across bilayer membranes via a primarily electroneutral process, although a cationic form of A23187 does carry some current.On the basis of fluorescence excitation spectra, A23187 can form either a 1:1 or 2:1 complex with Ca2+ in organic solvents. However, in biological membranes, only the 1:1 complexes with Ca2+, Mg2+, or Mn2+ are detected. A23187 produces fluorescent transients under conditions of Ca2+ uptake in sarcoplasmic reticulum, which appear to represent changes in intramembrane Ca2+ content. Changes in A23187 fluorescence due to mitochondrial Ca2+ accumulation are much smaller by comparison and fluorescence transients are not detected.Studies of A23187 fluorescence polarization and lifetimes in biological membranes allow a determination of the rotational correlation time (ρh) of the ionophore. In mitochondria at 22 °C, ρh is 11 nsec in the presence of Ca2+ and Mg2+, and less than 2 nsec in the presence of excess EDTA.The present results are consistent with a model of ionophore-mediated cation transport in which free M2+ binds with A23187 at the membrane surface to form the complex M(A23187)+. Reaction of this complex with another molecule of A23187 at the membrane surfaces results in the formation of electrically neutral M(A23187)2, which carries the divalent cation through the membrane.These results are discussed in terms of physical properties of biological membranes in regions in which divalent cation transport occurs. 相似文献
97.
H.Bruce Bosmann Kenneth R. Case Frank E. Young Anadi N. Chatterjee 《Biochemical and biophysical research communications》1974,57(4):1175-1179
Two strains of Staphylococcus aureus were investigated: S. aureus H, a normal wild-type strain, and 52A5, a mutant strain whose cell wall contains no teichoic acid but is made up entirely of mucopeptide. S. aureus H cells in the lag or stationary phase of growth had an electrophoretic mobility of ?1.10 μm/s/V/cm while those in the logarithmic phase had a mobility of ?0.80 μm/s/V/cm in saline at pH 7.2, 0.6 mM NaHCO3, 25°C (I = 0.145 g-ions/l). S. aureus 52A5 cells in the same solution had a mobility of ?0.87 μm/s/V/cm in lag and stationary growth phases but a mobility of ?1.30 μm/s/V/cm in the logarithmic growth phase. The S. aureus H cell surfaces at lag phase had pKs of 3.2 and 9.5; at logarithmic phase, 4.2 and 9.0; and at stationary phase, 3.0 and 9.5. The 52A5 cell surfaces at lag phase had pKs of 2.3 and 10.3; at logarithmic phase, 1.7 and 8.5; at stationary phase, 2.6 and 10.2. 相似文献
98.
Synaptic vesicles isolated from guinea-pig cerebral cortex had an electrophoretic mobility of -3.55mum.s(-1).V(-1).cm in saline-sorbitol, pH7.2, at 25 degrees C (ionic strength 0.015g-ions/1). The mobility was pH-dependent, varied with ionic strength and indicated that the vesicular surface contained weak acidic functions with a pK(a) in the range 3.0-3.8. Although the vesicular surface was determined to be highly negatively charged, treatment with neuraminidase had no effect on mobility and indicated that the relatively strong carboxyl groups of sialic acid do not contribute significantly to vesicular electrokinetic properties. Treatment of synaptic vesicles with trypsin or trypsinized concanavalin A resulted in increases in mobility, but treatment with ribonuclease, deoxyribonuclease, chrondroitinase ABC or hyaluronidase had no significant effect on mobility. Mn(2+) or Ca(2+) was more effective in decreasing vesicle mobility than was Mg(2+), Sr(2+) or Ba(2+). The electrokinetic properties of the synaptic vesicle surface are discussed and contrasted with the properties of the synaptosomal membrane. 相似文献
99.
100.
Norman M. Case 《Biotechnic & histochemistry》1953,28(3):155-158
Decalcification of 2-3 mm. sections of human ribs by 5-40% concentrations of both formic and nitric acid was subjected to a controlled study. The effect of adding 1 g. of phloroglucinol and of 2.5, 5 and 10 g. of the exchange resin (Win-3000) per 100 ml. of decalcifying solution was observed after staining celloidin sections with hematoxylin and Triosin or with Giemsa stain. Electrolytically decalcified material was included for comparison also. The following conclusions were drawn: (1) The addition of resin did not appreciably shorten the decalcification time nor enhance tissue preservation and staining qualities. (2) Formic acid, 20% or less, gave results superior to nitric acid in any concentration and also superior to those obtained after the electrolytic method. (3) The addition of 1% phloroglucinol to formic acid solution improved both preservation and staining. (4) Helly's fluid fixation with all combinations gave uniformly better results than formalin fixation. 相似文献