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Objective To explore the A2AR activation after traumatic brain injury mechanisms and the role of excessive tau protein phosphorylation.Methods With no specific mice experiment research of specific pathogens, position in the left parietal cortex in mice, by the method of controllable cortical against brain trauma model model, 15 min after injury in mice abdominal injection of A2AR specific inhibitors ZM241385 or use A2AR knockout mice, testing the brain neuron loss and tau protein phosphorylation level;Use specific agonists CGS21680 activate the original generation of nerve cells in the hippocampus and the A2AR human neuroblastoma cells, using immunocytochemistry and immunofluorescence test tua protein phosphorylation level of change, to observe axon transport function of mitochondria.Results Immunohistochemical results accumulation of optical density analysis showed that inhibition of A2AR activation can significantly reduce after cerebral trauma Ser404 tua protein loci phosphorylation levels, reduce excessive tua protein phosphorylation with nerve pathological change;A2AR activation after tua phosphorylation of proteins at a Ser404 site level increased significantly, nerve axons per unit length processes in the mitochondria number decreased significantly, resulting in axoplasmic transport dysfunction;To activate the original generation of nerve cells in the hippocampus and after the A2AR human neuroblastoma cells, tua protein phosphorylation Ser404 locus levels increased significantly.Conclusion A2AR activation after cerebral trauma has obvious influence on tua protein phosphorylation levels, may be a function by influencing the axoplasmic transport, eventually forming cognitive dysfunction.
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Objective To investigate the effect of mild hypothermia on expression of autophagyrelated proteins LC3 and Beclin-1 in the hippocampus of rats with traumatic brain injury (TBI).Methods Sixty healthy male adult SD rats were divided into sham group, TBI group, hypothermiatreated group (31-33℃) according to the random number, with 20 rats per group.Rat models of TBI were established using the Marmarou's method.After 4 h of normothermia or hypothermia, the rats were killed 6, 12, 24, and 48 h later.Co-localization of LC3 with neuron specific protein (NeuN) or mammalian target of rapamycinm (mTOR) was determined by double immunofluorescence.Levels of LC3, Beclin-1 and p-mTOR proteins were detected by Western blot analysis.Results LC3 co-localization with NeuN (or mTOR) was observed under confocal laser scanning microscope.In TBI group LC3 and Beclin-1 levels were seen to rise at 6 h, peaked at 24 h and fell slightly at 48 h, but the levels were still higher than these in sham group (P ＜ 0.05).In TBI group p-mTOR level began to decrease at 6 h, reached the lowest point at 12 h, and then ascended at 24 and 48 h, but the level was still lower than that in sham group (P ＜0.05).Mild hypothermia contributed to remarkable decreases in LC3 and Beclin-I expressions, while up-regulating p-mTOR after injury (P ＜ 0.05).Conclusion Mild hypothermia appears to be neuroprotective as it inhibits autophagy in hippocampal neurons after TBI in rats through activation of mTOR signaling pathway.
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Our earlier research has shown that mono-substituted N-phenyl-2, 2-dichloroacetamide exhibited much higher anti-cancer activity than the lead compound sodium dichloroacetate (DCA). In this paper, a variety of multi-substituted N-phenyl-2, 2-dichloroacetamides were synthesized and biologically evaluated. The results showed that 3, 5-disubstituted N-phenyl-2, 2-dichloroacetamide analogues had satisfactory potency. Among them, N-(3, 5-diiodophenyl)-2, 2-dichloroacetamide had an IC50 of 2.84 micromol x L(-1) against non-small cell lung cancer cell line A549 and could induce cancer cell apoptosis.
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Objective To examine ultrastructural features of the arteriole responsible for intracerebral hemorrhage or the perforating branches artery around hematoma in patients with hypertensive intracerebral hemorrhage and explore the mechanism of hypertensive intracerebral hemorrhage. Methods Twelve hypertensive patients with CT proved intracerebral hemorrhage underwent operation. The small artery specimens were obtained through cortex fistula and their ultrastructures were observed under the electron microscope. Results Twelve specimens including 4 cases of duty arteriolae and 8 cases of perforating branch arteriolae were collected, Different degrees of degeneration were observed in three layers of the arteriola in all 12 specimens. Changes in endothelial cells included endothelial cell necrosis, collapse, or fallen of from endomembrane, accompanied by degeneration of internal elastic membrane, such as uneven thickness, absence of intermittent and medial smooth muscle cell necrosis. Myofilaments in the cytoplasm were condensed to form a high electron-dense cytoplasm. No micro-aneurysm was observed. Conclusions The pathological changes of cerebral small artery walls load-bearing layer in hypertensive patients include internal elastic layer rupture, smooth muscle layer of degeneration, decreased elasticity and increased fragility. Small artery walls may rupture, resulting in bleeding under the condition of rapid dynamic changes of blood flow.
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Objective To study the effects of Xianlingqianggukoufuye (XLQGKFY) on postmenopausal osteoporosis in ovariectomized female rats. Method 60 female Sprague-dawley rats in 7-month were used, 50 of them were ovariectomized and randomly divided into 5 groups:ovariectomized (OVX), OVX+ Nylestriol, OVX+XLQGKFY (high dose, middle dose, low dose), the others were sham-operated group. Rats were treated with drugs starting at 3rd day after the operation for 90 days. Double in vivo fluorochrome labeling was administered to all rats. At the end-point of study, the blood was collected to detecte contents of ALP, StrACP in serum, the fourth lumar vertebra (LV4) and femur bone sections were cut and stained for bone histomorphometric analyses, biomechanical analyses and BMP analyses. Result XLQGKFY decreased greatly the StrACP content, increased bone stiffness, bone M-load, improved bone biomechanical property. Conclusion XLQGKFY has a good preventive effect on postmenopausal osteoporosis which provides for clinical use.