1 In the present study, the antiplatelet e ects and mechanisms of a new synthetic compound -indazole] were examined. 2 YD-3 inhibited the aggregation of washed rabbit platelets caused by thrombin (IC 50 =28.3 mM), but had no or little inhibitory e ect on that induced by arachidonic acid, collagen, platelet-activating factor (PAF) or U46619. YD-3 also suppressed generation of inositol phosphates caused by thrombin. On the other hand, thrombin-induced ®brin formation was not a ected by YD-3, indicating YD-3 does not inhibit the proteolytic activity of thrombin. 3 In washed human platelets, however, YD-3 had only mild inhibitory e ect on the low concentration (0.05 u ml 71 ) of thrombin-induced human platelet aggregation, and did not a ect that induced by higher concentrations (50.1 u ml 71 ) of thrombin or SFLLRN, the protease-activated receptor 1 (PAR1) agonist peptide. By contrast, YD-3 inhibited both human and rabbit platelet aggregation elicited by trypsin with IC 50 values of 38.1 mM and 5.7 mM, respectively. 4 YD-3, at 100 mM, had no e ect on ristocetin-induced glycoprotein Ib (GPIb)-dependent aggregation of human platelets. In addition, platelets treated with chymotrypsin, which cleaves GPIb, enhanced rather than attenuated the inhibition of YD-3 on thrombin-induced human platelet aggregation. These data indicate that GPIb plays no role in the antiplatelet e ect of YD-3. 5 In SFLLRN-desensitized human platelets, high concentration of thrombin (1 u ml 71 ) could still elicit intracellular Ca 2+ mobilization, and the rise of [Ca 2+ ] i was prevented by either leupeptin or YD-3. 6 Our results suggest that YD-3 inhibits a non-PAR1 thrombin receptor which mediates the major e ect of thrombin in rabbit platelets, but in human platelets, this receptor function becomes signi®cant only when the function of PAR1 has been blocked or attenuated.
Understanding how the brain functions is one of the grand challenges in modern scientific research. Similar to a computer, a functional brain is composed of hardware and software. The major bottleneck lies in the difficulty to directly observe the brain ‘software’, i.e. the rule and operating information used by the brain that might emerge from pan-neuron/synapse connectome. A recognized strategy for probing the functional connectome is to perform volumetric imaging in brains with high spatiotemporal resolution and deep brain penetration. Among various imaging technologies, optical imaging offers appealing combinations including spatial resolution of sub-micrometer to nanometer, temporal resolution of second to millisecond, penetration depth of millimeter or deeper, and molecular contrast based on the abundant choices of fluorescent indicators. Thus, it is ideal for enabling three-dimensional functional brain mapping of small animal models. In this review, we focus on recent technological advances in optical volumetric imaging, with an emphasis on the tools and methods for enhancing imaging speed, depth, and resolution. The review could serve as a quantitative reference for physicists and biologists to choose the techniques better suited for specific applications, as well as to stimulate novel technical developments to advance brain research.
BACKGROUNDVascular smooth muscle cell (VSMC) migration contributes to neointimal hyperplasia and restenosis after vascular injury. Gan‐Lu‐Yin (GLY), which is a traditional Chinese herbal medicine frequently prescribed to those patients with cancer, allergy, inflammation and also used as an immunoregulatory agent. To determine whether GLY possesses antimigratory properties, we stimulated rat VSMCs with 10% fetal bovine serum, and determined their molecular mechanisms related with migration properties. Also, animal experiments were conducted to determine if GLY could attenuate the neointima formation after balloon injury.METHODSVSMC were treated with different concentrations of GLY, and then analyzed with Flow cytometric analysis, zymography, transwell, and western blotting. SD rats subjected to balloon injury were stained with H&E.RESULTSBased on the results, we found that thickness of neointima was significantly attenuated by GLY. Non‐cytotoxic doses of GLY inhibited VSMCs migration was through its negative regulatory effects on phosphorylated ERK1/2, PI3K/AKT, and FAK. The data showed GLY has sufficient effects to inhibit the migration of VSMCs cells. In addition, GLY might block injury‐induced vascular neointima formation via the inhibition of VSMCs migration, without apoptosis.CONCLUSIONSThis study provides a better understanding of how GLY affects VSMC migration and its role in balloon injury‐induced neointima formation.
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