RESUMEN
Cisplatin (CDDP) has been widely used for glioblastoma treatment. miR-485-5p and E2F transcription factor 1 (E2F1) dysfunction has been reported in glioblastoma. Nonetheless, whether CDDP affects glioblastoma progression via the miR-485-5p-E2F1 axis requires investigation. The expression of miR-485-5p and E2F1 was investigated by quantitative real-time polymerase chain reaction or western blotting in glioblastoma tissues and cell lines. The interaction between miR-485-5p and E2F1 was confirmed using a luciferase assay. The malignancy of glioblastoma was detected using Cell Counting Kit-8, bromodeoxyuridine (BrdU), cell adhesion, flow cytometry, and transwell assays. We identified miR-485-5p downregulation and E2F1 upregulation in glioblastoma, and miR-485-5p inhibited cell growth and elevated cell apoptosis in glioblastoma cells after CDDP treatment. Moreover, miR-485-5p targeting E2F1 repressed cell growth and improved cell apoptosis in glioblastoma cells after CDDP treatment. Our study revealed that CDDP retarded glioblastoma cell development via the miR-485-5p-E2F1 axis, which may be a new direction for glioblastoma therapy.
Asunto(s)
Neoplasias Encefálicas/genética , Cisplatino/farmacología , Factor de Transcripción E2F1/genética , Glioblastoma/genética , MicroARNs/genética , Neoplasias Encefálicas/tratamiento farmacológico , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/tratamiento farmacológico , Humanos , MasculinoRESUMEN
Purpose: Homer1a is a member of the post-synaptic density protein family that plays an important role in neuronal synaptic activity and is extensively involved in neurological disorders. The aim of this study is to investigate the role of Homer1a in modulating neuronal survival using an in vitro traumatic neuronal injury model.Materials and methods: Neurons were extracted from rats and identifited. Then, the cells were treated with Homerla overexpression or interference vectors. Western blot was performed to evaluate the expression of Homerla, apoptosis-related proteins(caspase3, caspase8, caspase9, Fasl, Bax, and p53), autophagy-related proteins (LC3ll and Beclin1), and the activiation of PI3K/AKT/mTOM pathway. In addition, the cell viability and apoptosis rate were measured. Results: After transfection with overexpression or interference vectors, the mRNA and protein expression of Homer1a increased or decreased significantly, respectively. Upregulation of Homer1a significantly alleviated apoptosis and enhanced cell viability and autophagy after traumatic neuronal injury. Homer1a overexpression also significantly decreased the expression of the pro-apoptosis proteins caspase 3, caspase 8, caspase 9, Fasl, Bax, and p53 in neurons. Furthermore, neuron autophagy was increased after traumatic neuronal injury as demonstrated by the greater accumulation of autophagosomes and higher expression of LC3II and Beclin1 induced by Homer1a overexpression. In addition, Homer1a overexpression inhibited the activation of PI3K/AKT/mTOR signaling. Conclusion: These findings indicated that Homer1a potentially protects neurons from traumatic injury by regulating apoptosis and autophagy via the caspase and PI3K/AKT/mTOR signaling pathways and may be an effective intervention target in traumatic brain injury.
Asunto(s)
Lesiones Encefálicas/metabolismo , Proteínas de Andamiaje Homer/metabolismo , Neuronas/metabolismo , Animales , Apoptosis , Proliferación Celular , Femenino , Fosfatidilinositol 3-Quinasa/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
The efficacy and applied value of endoscopic hematoma evacuation vs. external ventricular drainage (EVD) in the treatment of severe ventricular hemorrhage (IVH) were explored and compared. From Jan. 2015 to Dec. 2016, the clinical data of 42 cases of IVH were retrospectively analyzed, including 18 patients undergoing endoscopic hematoma evacuation (group A), and 24 patients receiving EVD (group B). The hematoma clearance rate was calculated by 3D Slicer software, and complications and outcomes were compared between the two groups. There were no significant differences in age, sex and Graeb score between groups A and B (P>0.05). The hematoma clearance rate was 70.81%±27.64% in group A and 48.72%±36.58% in group B with a statistically significant difference (P<0.05). The operative time in groups A and B was 72.45±25.26 min and 28.54±15.27 min, respectively (P<0.05). The Glasgow Coma Scale (GCS) score increased from 9.28±2.72 at baseline to 11.83±2.91 at 1 week postoperatively in group A, and from 8.25±2.62 at baseline to 10.79±4.12 at 1 week postoperatively in group B (P<0.05). The length of hospital stay was 12.67±5.97 days in group A and 17.33±8.91 days in group B with a statistically significant difference (P<0.05). The GOS scores at 6 months after surgery were 3.83±1.12 in group A, and 2.75±1.23 in group B (P<0.05). These results suggested that endoscopic hematoma evacuation has an advantage of a higher hematoma clearance rate, fewer complications and better outcomes in the treatment of severe IVH, indicating it is a safe, effective and promising approach for severe IVH.
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Hemorragia Cerebral Intraventricular/cirugía , Ventrículos Cerebrales/cirugía , Drenaje/métodos , Endoscopía/métodos , Anciano , Hemorragia Cerebral Intraventricular/fisiopatología , Ventrículos Cerebrales/fisiopatología , Drenaje/efectos adversos , Endoscopía/efectos adversos , Femenino , Fibrinolíticos/administración & dosificación , Escala de Coma de Glasgow , Hematoma/fisiopatología , Hematoma/cirugía , Humanos , Inyecciones Intraventriculares , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Posttraumatic stress disorder (PTSD) is characterized by reexperiencing of a traumatic event, avoidance of traumaassociated stimulation, general changes in mood and cognition, and hyper arousal symptoms. Cyclooxygenase is involved in the production of prostaglandins and thromboxanes, and its inducible form cyclooxygenase2(COX2), an important mediator of cell injury in inflammation, is primarily expressed in leukocytes and brain cells. The present study investigated the expression of COX2 in the hippocampi of rats with PTSD and evaluated the effect of COX2 inhibition on PTSD. Adult male Wistar rats were randomly divided into three groups: Control (n=20), PTSD (n=20) and intervention group (PTSD+COX2 inhibitor treatment, n=20). The expression of COX2 was detected by immunohistochemistry, reverse transcriptionquantitative polymerase chain reaction and western blotting. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining was used to observe the apoptosis of rat hippocampal neurons. Tumor necrosis factor α (TNFα), interleukin (IL)6 and prostaglandin E2 (PGE2) levels were analyzed by ELISA. Nitric oxide (NO) was detected using the Griess test. The behavioral and cognitive function of rats in the PTSD group was significantly decreased compared with the control group, while the behavioral and cognitive function of rats in the intervention group were improved. The COX2 mRNA and protein expression levels in hippocampi of rats in the PTSD group were higher than in the control and intervention group. The apoptosis of hippocampus in rats with PTSD was significantly increased compared with the control group and following treatment with COX2 inhibitor, apoptosis was decreased. In addition, compared with the control group and intervention group, the levels of TNFα, IL6, PGE2 and NO in hippocampi of rats were increased in the PTSD group. The present study indicated that COX2 may be involved in the pathogenesis of PTSD, and inhibition of its expression serves a neuroprotective role in hippocampi of PTSD rats.
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Inhibidores de la Ciclooxigenasa 2/farmacología , Ciclooxigenasa 2/metabolismo , Trastornos por Estrés Postraumático/etiología , Trastornos por Estrés Postraumático/metabolismo , Animales , Apoptosis , Conducta Animal , Biomarcadores , Ciclooxigenasa 2/genética , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Expresión Génica , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Inmunohistoquímica , Interleucina-6/metabolismo , Masculino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Trastornos por Estrés Postraumático/psicología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Objective: To compare the clinical effects of inguinal varicocelectomy, Palomo varicocelectomy,laparoscopic varicocelectomy, and microscopic varicocelectomy in the treatment of varicocele. Methods: We retrospectively analyzed the pre- and post-operative clinical data about 318 cases of varicocele,108 treated by inguinal varicocelectomy,84 by Palomo varicocelectomy,68 by laparoscopic varicocelectomy, and 58 by microscopic varicocelectomy. We compared the operation time, hospital stay, pre- and post-operative sperm concentration and progressive motility, incidence of complications, rate of recurrence, and rate of sperm quality improvement among the four groups. Results: The operation times for the inguinal, Palomo, laparoscopic, and microscopic varicocelectomy procedures were(50. 3 ± 13. 9),(70. 4 ± 14. 3),(35. 1 ± 11. 1),and(65. 3 ± 13. 2) min, respectively, significantly shorter for the laparoscopic strategy than for the other three( P < 0. 05). The lengths of hospital stay of the four groups of patients were(6. 3 ± 1. 6),(5. 7 ± 1. 5),(4. 3 ± 1. 4),and(3. 4 ± 1. 3) d, respectively, remarkably shorter in the microscopic group than in the other three( P < 0. 05). The microscopic group also showed a significantly lower rate of postoperative complications, incidence of spermatic vein reflux, and recurrence( P < 0. 05) and higher rates of improvement in postoperative sperm concentration and progressive motility than the other three groups( P < 0. 05). Conclusion: Microscopic varicocelectomy is superior to inguinal,Palomo and laparoscopic varicocelectomy procedures in the treatment of varicocele for its lower incidence of complications, higher rate of sperm quality improvement,and shorter length of hospital stay. It is therefore more suitable to be applied in community hospitals.
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Varicocele/cirugía , Procedimientos Quirúrgicos Vasculares/métodos , Humanos , Laparoscopía , Tiempo de Internación , Masculino , Tempo Operativo , Complicaciones Posoperatorias , Periodo Posoperatorio , Recurrencia , Estudios Retrospectivos , Recuento de Espermatozoides , Espermatozoides , Resultado del Tratamiento , VenasRESUMEN
OBJECTIVE: Nogo-A is an axon regeneration inhibitor, and its function in central nervous system (CNS) is still unknown. The present study is to explore the relationship between the expression of Nogo-A and the malignancy of oligodendroglial tumors in patients. METHODS: Tumor tissue samples with different malignancy grade were obtained from the hospitals. The samples used for detection had been diagnosed as oligodendroglial tumors (oligodendroglioma or anaplastic oligodendroglioma). The expression of Nogo-A was detected by immunohistochemistry and western-blot analysis. The correlation test between the Nogo-A expression and the morphological changes (the percentages of atypical cells and mitotic cells in the tumors) related to the malignancy of tumor tissues was performed. RESULTS: There was significant negative correlation between the Nogo-A expression and the morphological change of tumor tissues according to immunohistochemistry. Western-blot analysis also indicated that the gray value of Nogo-A protein band in the oligodendroglioma group was significantly higher than that in the anaplastic oligodendroglioma group. CONCLUSION: Nogo-A expression was negatively correlated with the malignancy grade of oligodendroglial tumors.