ABSTRACT
HuR (human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescence polarization (FP) based high-throughput screening (HTS) system, the clinically used drug eltrombopag was identified. Activity of eltrombopag on molecular level was verified with FP, electrophoretic mobility shift assay (EMSA), simulation docking and surface plasmon resonance (SPR). Further, we showed that eltrombopag inhibited cell proliferation of multiple cancer cell lines and macrophages, and the anti-tumor activity was also demonstrated in a 4T1 tumor-bearing mouse model. The data showed that eltrombopag was efficient in reducing microvessels in tumor tissues. We then confirmed the HuR-dependent anti-angiogenesis effect of eltrombopag in 4T1 cells and RAW264.7 macrophages with qRT-PCR, HuR-overexpression and HuR-silencing assays, RNA stability assays, RNA immunoprecipitation and luciferase assays. Finally, we analyzed the anti-angiogenesis effect of eltrombopag on human umbilical vein endothelial cells (HUVECs) mediated by macrophages with cell scratch assay and Matrigel angiogenesis assay. With these data, we revealed the HuR-dependent anti-angiogenesis effect of eltrombopag in breast tumor, suggesting that the existing drug eltrombopag may be used as an anti-cancer drug.
ABSTRACT
Objective To investigate the intelligence development status of the low birth weight infants and its influence factors. Methods The intelligence developments of 135 low birth weight infants aged 6-30 months were investigated using Bayley Scales of Infant Development, and the self-development influential factors were analyzed with questionnaire.Results The average of MDI was 86.76±18.95 in 135 infants,of which the detection rate of MDI<80 points accounted for 17.8%and the detection rate of PDI<80 points accounted for 29.6%;birth weight of infant,age,the degree of parents,culture and feeding way had significant effects on MDI in infants;age and birth weight had significant effects on PDI in infants. Conclusion The development level of infants is influenced by multi-factors. More attention should be paid to reduce premature and low birth weight infants,improve the degree of parents' culture, advocate breastfeeding and conduct early intervention in order to assure the intelligence development of infants.
ABSTRACT
Neural transplantation is a promising treatment strategy that can restore the motor, sensory and cognitive functions in the rat middle cerebral artery occlusion (MCAO) model of stroke. In particular, neuronal cells derived from a human teratocarcinoma cell line, called hNT neurons or LBS neurons (clinical grade preparation), are effective in improving behavioral recovery after stroke. In the elderly, epilepsy is a common sequela of stroke, especially if the infarction involves cerebral cortex. However, the effect of implanting neural cells on seizure susceptibility in the MCAO model has not yet been determined. The purpose of this study was to determine the susceptibility to pentylenetetrazol (PTZ)-induced seizures in normal, MCAO-lesioned and MCAO-lesioned rats in which the LBS neurons were injected. Adult, male Sprague-Dawley rats were subjected to 60 min of MCAO using the intraluminal filament technique followed 3-4 weeks later by transplantation of 80,000 LBS-neurons into the ipsilateral cortex. Susceptibility to PTZ-induced seizures was tested 4-6 weeks post-transplant at doses of 35, 50 and 70 mg/kg, administered subcutaneously. Latency to the first lethal response, latency to first generalized seizure, duration of the first generalized seizure, and the number of generalized seizures in an hour post-PTZ treatment observation period was determined. Even thought there was a tendency for groups that underwent MCAO to be more susceptible to seizures, there were no statistically significant differences between the groups and no differences between MCAO alone and MCAO animals in which cells had been implanted. While grafted cells were identified in all but one injected animal, the results suggest that the grafts may not have been healthy either from immunological rejection or PTZ-induced injury. These results suggest that while placing cells within the cortex does not reduce seizure susceptibility, it also does not increase the incidence of seizures. Further investigations are warranted.
ABSTRACT
OBJECTIVE: To explore the expression of mRNA and its protein in burned rats and their effects on burn wound healing. METHODS: A partial-thickness burn of 30% total body surface ar ea was created on the back of 40 Wistar rats. In situ hybridization and immunohi stochemical methods were used to evaluate the location and the amount of the c-fos mRNA and its protein in normal skin and the burned skin, respectively, at 3 h, 6 h, 1 d, 3 d, 7 d and 14 d after burn. RESULTS: Under a light microscope, both the expression of c-fo s mRNA and its protein could be found in the normal skin, but their induction le vels were much higher in the burned skin. The level of fos protein expression reached peak at 3 h after burn while that of c-fos mRNA reached peak at 6 h aft er burn. CONCLUSIONS: The expression of c-fos can be induced by burns. And the peak level expression of c-fos mRNA comes later than that of c-fos p rotein. It indicates that the action of fos protein is induced by post-translat ional modification of pre-existing fos molecules.
