RESUMEN
The object of this study was to explore the effect of rapamycin regulating the proliferation of Schwann cells through activating the extracellular signal-regulated kinase (ERK) signaling pathway on rats with spinal cord injury (SCI). The rat Schwann cells were cultured and divided into solvent (DMSO) group, rapamycin (Rapa) group (1.5 nM, 3.0 nM, 6.0 nM, 12.0 nM, 24.0 nM and 48.0 nM), and Rapa + ERK inhibitor (PD98059) group (40 mM). The proliferation of Schwann cells was detected by MTS. Western blot was used to evaluate the expression of ERK and p-ERK protein. Moreover, the spinal cord compression injury rat model was established, and the rats were divided into normal control group, SCI group and Schwann cell transplantation group. The animal experiment ended 7 weeks after Schwann cells had been injected every day into the injured rats. In the second animal experiment, the rats were divided into DMSO group, Rapa group and Rapa + PD98059 group. The motor recovery of rats was evaluated using the Basso-Beattie-Bresnahan (BBB) score every week, and the proliferation of Schwann cells at the site of SCI was detected using immunohistochemistry. It was verified that lowdose rapamycin (1.5 nM) could significantly promote the proliferation of Schwann cells cultured in vitro (P<0.001), most significantly at 48 h. Rapamycin could activate the ERK signaling pathway. The results of the first animal experiment showed that the BBB score in Schwann cell transplantation group rose with time compared with that in SCI group (P<0.05). The BBB score was obviously increased in Rapa group compared with that in DMSO group and Rapa + PD98059 group (P<0.05). According to the results of Ki67 immunohistochemistry, the proliferation ability of Schwann cells at the site of SCI was remarkably stronger than that in the other two groups. Rapamycin regulates the proliferation of Schwann cells through the ERK signaling pathway. The proliferation of Schwann cells can effectively repair the damaged nerve cells and neurological function in SCI rats.
Asunto(s)
Traumatismos de la Médula Espinal , Animales , Quinasas MAP Reguladas por Señal Extracelular , Sistema de Señalización de MAP Quinasas , Neuronas , Ratas , Ratas Sprague-Dawley , Recuperación de la Función , Transducción de Señal , Sirolimus/farmacología , Médula Espinal , Traumatismos de la Médula Espinal/tratamiento farmacológicoRESUMEN
OBJECTIVE: This work aimed to study the mechanism of lncRNATCF7 upregulating DNMT1 mediated by HPV-18 E6 and regulating the biological behavior of cervical cancer cells by inhibiting miR-155. PATIENTS AND METHODS: HPV-16 E6 enhanced DNMT1 expression in cervical cancer cells, which was detected by Western blotting. The expression of miR-155 in cervical cancer was detected by qPCR, the interaction between TCF-7 and miR-155 by Dual-luciferase reporter gene. The changes in invasion ability of cervical cancer cells and the effect of miR-155 on the invasion ability of cervical cancer cells after inhibiting TCF-7 were detected by the transwell invasion assay, while changes in migration ability of cervical cancer cells and the effect of miR-155 on migration ability of cervical cancer cells after inhibiting TCF-7 were observed by the scratch assay. The effect of inhibiting TCF-7 on the tumor size and volume of cervical cancer was detected by the subcutaneous tumor formation in nude mice. RESULTS: E6 expression was significantly inhibited by E6 siRNA. The knockdown of endogenous HPV-16 E6 markedly inhibited the expression of DNMT1; TCF-7 specifically bound to the 3' UTR of miR-155; inhibition of TCF-7 can inhibit invasion and migration of cervical cancer cells; enhanced miR-155 after the inhibition of TCF-7 can promote the invasion and migration of cervical cancer cells; compared with NC group, the tumor volume and weight of TCF-7-siRNA group tumor-bearing was significantly reduced. CONCLUSIONS: TCF-7 plays an important role in the development of cervical cancer. TCF-7 can target miR-155 to regulate the invasion and migration of cervical cancer cells.
Asunto(s)
ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , MicroARNs/metabolismo , Proteínas Oncogénicas Virales/metabolismo , ARN Largo no Codificante/metabolismo , Proteínas Represoras/metabolismo , Regiones no Traducidas 3' , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , ADN (Citosina-5-)-Metiltransferasa 1/antagonistas & inhibidores , ADN (Citosina-5-)-Metiltransferasa 1/genética , Femenino , Humanos , Ratones , Ratones Desnudos , MicroARNs/genética , Proteínas Oncogénicas Virales/antagonistas & inhibidores , Proteínas Oncogénicas Virales/genética , Interferencia de ARN , ARN Largo no Codificante/antagonistas & inhibidores , ARN Largo no Codificante/genética , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/uso terapéutico , Proteínas Represoras/antagonistas & inhibidores , Proteínas Represoras/genética , Regulación hacia Arriba , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Ensayos Antitumor por Modelo de XenoinjertoAsunto(s)
Acné Vulgar/tratamiento farmacológico , Anticonceptivos Orales/uso terapéutico , Acetato de Ciproterona/uso terapéutico , Etinilestradiol/uso terapéutico , Infarto/inducido químicamente , Tromboembolia/etiología , Adulto , Médula Cervical/patología , Anticonceptivos Orales/efectos adversos , Acetato de Ciproterona/efectos adversos , Imagen de Difusión por Resonancia Magnética , Combinación de Medicamentos , Etinilestradiol/efectos adversos , Femenino , Humanos , Infarto/complicaciones , Dolor de Cuello/etiología , Resultado del TratamientoRESUMEN
A high precision high voltage divider has been developed for the electron beam ion trap in Shanghai. The uncertainty caused by the temperature coefficient of resistance (TCR) and the voltage coefficient of resistance has been studied in detail and was minimized to the level of ppm (10(-6)) range. Once the TCR was matched between the resistors, the precision of the dividing ratio finally reached the ppm range also. We measured the delay of the divider caused by the capacitor introduced to minimize voltage ripple to be 2.35 ms. Finally we applied the divider to an experiment to measure resonant energies for some dielectronic recombination processes for highly charged xenon ions. The final energies include corrections for both space charge and fringe field effects are mostly under 0.03%.
