ABSTRACT
Objective: To investigate the effect of memantine on Parkinson's disease cell models. Methods: Parkinson's disease cell models were established using PC12 cells incubated with 6-hydroxydopamine (6-OHDA). Flow cytometry and microscopy were used to investigate the apoptotic process and the percentage of different apoptotic stages. PC12 cells were infected with lentiviral vectors to knockdown Nur77. Western blotting was used to detect the expression of Nur77 and caspase -3, -8, -9, -12 in PC12 cells withdifferent concentrations of 6-OHDA or 6-OHDA+memantine. Results: 6-OHDA led to apoptosis PC12 cells, and increased the expression of Nur77 and caspases. Memantine significantly inhibited 6-OHDA-induced apoptosis of PC12 cells. Meanwhile, memantine could mitigate apoptosis of PC12 cells by regulating the Nur77 and caspase pathway. Conclusions: Memantine has a protective effect on the PC12 cell model via regulating the Nur77 and caspases pathway.
ABSTRACT
The aim of this paper was to study the effect of total flavones of Clematis filamentosa Dunn(TFCD) post-conditioning against myocardial ischemia-reperfusion injury (MIRI) and the role of PI3K/Akt-eNOS signaling pathway. Forty male SD rats were divided randomly into five groups: Sham group, model group (I/R), TFCD post-conditioning group (TFCD), TFCD post-condition-ing+LY294002 (a PI3K/Akt signaling pathway inhibitor) group (TFCD+LY), and LY294002 group (LY). At the end of reperfusion, hemodynamic parameters were recorded, morphology changes of myocardial tissue were evaluated by using HE staining, and myocardial infarct size were observed, blood samples were obtained to determine plasma activation of lactate dehydrogenase (LDH), creatine kinase (CK) nitric oxide (NO), endothelial nitric oxide synthase (eNOS), superoxide dismutase (SOD), maleic dialdehyde (MDA) and glutathione peroxidase (GSH-Px). The expressions of Akt, p-Akt, eNOS and p-eNOS proteins were assessed by using Western blot, and eNOS and inducible nitric oxide synthase (iNOS) mRNA was measured by RT-PCR. The results showed that, compared with the model group, TFCD post-conditioning remarkably improved hemodynamics function and myocardial structure, reduced myocardial infarct size and enhanced the contents of NO, eNOS, SOD and GSH-Px, and decreased the contents of LDH, CK and MDA, increased the levels of phosphorylation of Akt and eNOS protein expression, eNOS and iNOS mRNA expression significantly(P＜0.05 or P＜0.01). These effects were inhibited by LY294002, a blocker of PI3K/Akt signaling pathway. The above experiments indicated that TFCD post-conditioning could significantly reduce MIRI in rats, the mechanism of which may be associated with increasing antioxidation, scavenging oxygen free radicals, regulating NO generation and activating PI3K/Akt-eNOS signaling pathway.
Subject(s)
Animals , Male , Rats , Clematis , Flavones , Myocardial Reperfusion Injury , Nitric Oxide Synthase Type III , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Rats, Sprague-Dawley , Signal TransductionABSTRACT
<p><b>OBJECTIVE</b>To investigate the mechanism and management of multiple urethral metastases from prostate adenocarcinoma after radical prostatectomy.</p><p><b>METHODS</b>We summed up the experience in the management of a case of multiple urethral metastases from prostate adenocarcinoma after radical prostatectomy and reviewed relevant literature. The patient was a 79-year-old male, who had received radical prostatectomy for prostate adenocarcinoma 13 years before, and presented with macrohematuria and dysuria in the past 2 weeks. A nodule (1.0 x 0.5 cm) was found in the urethral meatus. Cystourethroscopy revealed multiple tumors in the urethra and biopsy indicated them to be metastases from prostate adenocarcinoma. The preoperative level of PSA was 3.01 microg/L. As treatment, we performed radical urethrectomy and cystostomy.</p><p><b>RESULTS</b>Postoperative pathology showed multiple metastases of prostate adenocarcinoma to the urethra, involving the urethral sphincter and corpus spongiosum. Immunohistochemistry revealed PSA (+), PsAP(+), AR(+) and CK 7(-). The surgical margin was negative. The patient recovered well postoperatively, with a PSA level of 1.00 microg/L.</p><p><b>CONCLUSION</b>Urethral metastasis of prostate adenocarcinoma after radical prostatectomy is rarely seen clinically. For the treatment of multiple urethral metastases, surgery is the first choice and radical urethrectomy is an appropriate management.</p>