Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
1.
Br J Neurosurg ; 37(5): 1395-1397, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33377403

RESUMEN

We report a case of cholesteatoma that caused left facial pain with facial numbness. The tumour was located in the left cerebellopontine angle (CPA) and Meckel's cave. A balloon was first placed into Meckel's cave, and then, under electrophysiological monitoring, the tumour within the CPA cistern was resected via the retrosigmoid approach. The balloon was inflated in Meckel's cave to push the tumour out of Meckel's cave, and then, the tumour was completely removed under endoscopy. The symptoms, including pain and numbness, subsided after surgery.


Asunto(s)
Colesteatoma , Neoplasias , Neuroendoscopía , Humanos , Ángulo Pontocerebeloso/diagnóstico por imagen , Ángulo Pontocerebeloso/cirugía , Colesteatoma/cirugía , Hipoestesia/cirugía , Femenino , Persona de Mediana Edad
2.
Acta Pharmacol Sin ; 42(1): 108-114, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32398685

RESUMEN

Glioblastoma (GBM) patients have extremely poor prognoses, and currently no effective treatment available including surgery, radiation, and chemotherapy. MAPK-interacting kinases (MNK1/2) as the downstream of the MAPK-signaling pathway regulate protein synthesis in normal and tumor cells. Research has shown that targeting MNKs may be an effective strategy to treat GBM. In this study we investigated the antitumor activity of osimertinib, an FDA-approved epidermal growth factor receptor (EGFR) inhibitor, against patient-derived primary GBM cells. Using high-throughput screening approach, we screened the entire panel of FDA-approved drugs against primary cancer cells derived from glioblastoma patients, found that osimertinib (3 µM) suppressed the proliferation of a subset (10/22) of EGFR-negative GBM cells (>50% growth inhibition). We detected the gene expression difference between osimertinib-sensitive and -resistant cells, found that osimertinib-sensitive GBM cells displayed activated MAPK-signaling pathway. We further showed that osimertinib potently inhibited the MNK kinase activities with IC50 values of 324 nM and 48.6 nM, respectively, against MNK1 and MNK2 kinases; osimertinib (0.3-3 µM) dose-dependently suppressed the phosphorylation of eukaryotic translation initiation factor 4E (eIF4E). In GBM patient-derived xenografts mice, oral administration of osimertinib (40 mg· kg-1 ·d-1, for 18 days) significantly suppressed the tumor growth (TGI = 74.5%) and inhibited eIF4E phosphorylation in tumor cells. Given the fact that osimertinib could cross the blood-brain barrier and its toxicity was well tolerated in patients, our results suggest that osimertinib could be a new and effective drug candidate for the EGFR-negative GBM patients.


Asunto(s)
Acrilamidas/uso terapéutico , Compuestos de Anilina/uso terapéutico , Antineoplásicos/uso terapéutico , Glioblastoma/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Inhibidores de Proteínas Quinasas/uso terapéutico , Adolescente , Adulto , Anciano , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Niño , Receptores ErbB/deficiencia , Factor 4E Eucariótico de Iniciación/química , Factor 4E Eucariótico de Iniciación/metabolismo , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Masculino , Ratones , Persona de Mediana Edad , Fosforilación/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Ensayos Antitumor por Modelo de Xenoinjerto , Adulto Joven
3.
Br J Neurosurg ; 35(3): 280-284, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32619112

RESUMEN

OBJECTIVE: To investigate the efficacy and safety of percutaneous balloon compression (PBC) for the treatment of trigeminal neuralgia in elderly patients. Methods: We retrospectively analysed data of 105 elderly patients with primary trigeminal neuralgia who were over 70 years and underwent percutaneous balloon compression using anatomic positioning and imaging guidance from January 2019 to November 2019. Results: The immediate cure rate of pain in this group of patients was 97.1% (Barrow Neurological Institute (BNI) pain scores: class I and II; numbness score: class II). Postoperative keratitis was reported in 1 patient, masticatory muscle weakness and muscle atrophy in 1 patient, herpes labialis in 8 patients and lacunar infarction in 2 patients. Facial numbness and decreased sensation occurred in patients with significant pain relief. No serious complications were reported. There was no statistically significant difference in efficacy between the short compression and long compression time groups. Conclusion: PBC is a safe and effective approach to treat trigeminal neuralgia.


Asunto(s)
Neuralgia del Trigémino , Anciano , Humanos , Dolor , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Neuralgia del Trigémino/cirugía
4.
Epilepsy Behav ; 88: 81-86, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30243110

RESUMEN

PURPOSE: Epilepsy is considered a disorder of neural networks. Patients diagnosed with refractory epilepsy frequently experience attention impairments. Seizure activity in epilepsy may disturb brain networks and damage the brain function of attention. The aims of this study were to assess functional and causal connectivities of the attention networks and default mode network using resting-state functional magnetic resonance imaging (fMRI). METHOD: Resting-state fMRI data were gathered from 19 patients with refractory epilepsy (mixed localization and aetiologies) and 21 healthy people. The fMRI data were analyzed by group independent component analysis (ICA) fMRI toolbox to extract dorsal attention network (DAN), ventral attention network (VAN), and default mode network (DMN). The components of the selected networks were compared between patients and healthy controls to explore the change in functional connectivity (FC). Granger causality analysis was performed by taking the aforementioned significant brain areas as regions of interest (ROIs) to calculate autoregression coefficients of each pair of ROIs. Comparisons were done to find the significantly different causal connectivity when FC was changed between patients and healthy controls. RESULTS: In DAN, the FC values of the bilateral frontal eye field (FEF) and left intraparietal sulcus (IPS) were decreased. In VAN, the FC values of the double-side ventral prefrontal cortex (vPFC) and the temporoparietal junction (TPJ) were reduced. As for DMN, the FC values of the bilateral medial prefrontal cortices (mPFC) were decreased whereas those for the bilateral precuneus (PCUN) were increased. Granger causal connectivity values were correlated: causal influence was decreased significantly from the left IPS (in DAN) to the double side of the vPFC but remained the same for the right FEF (in DAN) to the right TPJ. The value was decreased from the left PCUN (in DMN) to the right TPJ and FEF, and the causal flow from the right PCUN to the right TPJ and bilateral vPFC was also significantly inhibited (p < 0.05). CONCLUSION: Frequent seizures in patients with refractory epilepsy may damage the cortex and disturb DAN, VAN, and DMN, leading to functional and causal connectivity alteration. In addition, epileptic activity may disrupt network interactions and further influence information communication.


Asunto(s)
Atención/fisiología , Mapeo Encefálico , Corteza Cerebral/fisiopatología , Epilepsia Refractaria/fisiopatología , Imagen por Resonancia Magnética , Red Nerviosa/fisiopatología , Adulto , Estudios de Casos y Controles , Corteza Cerebral/diagnóstico por imagen , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/psicología , Femenino , Humanos , Masculino , Red Nerviosa/diagnóstico por imagen
5.
Neurol Sci ; 35(8): 1275-80, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24633814

RESUMEN

Progressive dopamine neuron degeneration in the substantia nigra pars compacta is considered the most prominent pathological characteristic of Parkinson's disease (PD). Currently, there is no cure, but only the capability to relieve the symptoms of PD. The conserved dopamine neurotrophic factor (CDNF) protects and rescues dopamine neurons in vivo. However, the molecular function of CDNF in PD remains unclear. In present study, we investigated the role and intrinsic mechanism of CDNF in preventing and reversing rat pheochromocytoma (PC12) cells from apoptosis induced by 6-hydroxydopamine (6-OHDA). We demonstrate that 6-OHDA induces cell death in PC12 cells, but that CDNF attenuates this effect in a dose-dependent manner. Further study shows that upregulation of the Bcl-2/Bax ratio and downregulation of caspase-3 activity are observed in a dose-dependent manner upon pre-treatment or post-treatment with CDNF, suggesting a pathway of regulation of apoptosis by CDNF. These data demonstrate that CDNF prevents the apoptosis of PC12 cells induced by 6-OHDA by modulating Bcl-2/Bax and caspase-3 activation.


Asunto(s)
Caspasa 3/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Factores de Crecimiento Nervioso/farmacología , Oxidopamina/toxicidad , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Neoplasias de las Glándulas Suprarrenales/patología , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/genética , Neuronas Dopaminérgicas/citología , Neuronas Dopaminérgicas/metabolismo , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Inducción Enzimática/efectos de los fármacos , Genes bcl-2 , Fármacos Neuroprotectores/farmacología , Células PC12 , Feocromocitoma/patología , Proteínas Proto-Oncogénicas c-bcl-2/genética , ARN Mensajero/biosíntesis , ARN Neoplásico/biosíntesis , Ratas , Proteínas Recombinantes/farmacología , Proteína X Asociada a bcl-2/genética
6.
Zhonghua Yi Xue Za Zhi ; 92(15): 1033-6, 2012 Apr 17.
Artículo en Zh | MEDLINE | ID: mdl-22781643

RESUMEN

OBJECTIVE: To explore the brain regions associated with impulsive decision-making behaviors and interpret the nervous mechanism for addiction and relapse in heroin abusers. METHODS: Using the paradigms of psychological experiment, the subjects in both heroin addiction group (HA group) and normal control group (HC group) performed Iowa gambling task (IGT) and simultaneously underwent functional magnetic resonance imaging (fMRI) scan. All the above data were gathered and then analyzed by SPM5 software to explore both the brain regions and their functional changes correlated with impulsive decision-making. RESULTS: Evidence by IGT behavioral consequences demonstrated that the net scores in HC group increased with numbers of decision-making whereas no increment (fluctuating between-1 and 0) was observed in HA group. Based on the results of fMRI analysis, right orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), left ventromedial prefrontal cortex (MPFC) and anterior cingulate cortex (ACC) were activated in both groups. But the right OFC was more active while the right DLPFC and left MPFC were weaker in HA group versus the HC group. Meanwhile, activation of right lenticular nucleus, right thalamus, right insula, hippocampus and left caudate nucleus were observed in HA group. CONCLUSION: Heroin abusers are incapable of impulsive decision-making in behavioral studies. Such a brain region as prefrontal cortex participates in the decision-making performance and control of impulsiveness. Functionally abnormal brain regions correlated with impulsive decision-making may be one cause of genesis, maintenance and relapse of heroin addiction.


Asunto(s)
Toma de Decisiones/efectos de los fármacos , Dependencia de Heroína/fisiopatología , Dependencia de Heroína/psicología , Conducta Impulsiva , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Corteza Prefrontal/fisiopatología , Adulto Joven
7.
Zhonghua Yi Xue Za Zhi ; 92(45): 3221-3, 2012 Dec 04.
Artículo en Zh | MEDLINE | ID: mdl-23328472

RESUMEN

OBJECTIVE: To explore the possible brain mechanism of online game addiction (OGA) in terms of brain morphology through voxel-based morphometric (VBM) analysis. METHODS: Seventeen subjects with OGA and 17 age- and gender-matched healthy controls (HC group) were recruited from Department of Psychology at our hospital during February-December 2011. The internet addiction scale (IAS) was used to measure the degree of OGA tendency. Magnetic resonance imaging (MRI) scans were performed to acquire 3-dimensional T1-weighted images. And FSL 4.1 software was employed to confirm regional gray matter volume changes. For the regions where OGA subjects showed significantly different gray matter volumes from the controls, the gray matter volumes of these areas were extracted, averaged and regressed against the scores of IAS. RESULTS: The OGA group had lower gray matter volume in left orbitofrontal cortex (OFC), left medial prefrontal cortex (mPFC), bilateral insula (INS), left posterior cingulate cortex (PCC) and left supplementary motor area (SMA). Gray matter volumes of left OFC and bilateral INS showed a negative correlation with the scores of IAS (r = -0.65, r = -0.78, P < 0.05). CONCLUSION: Gray matter volume changes are present in online game addicts and they may be correlated with the occurrence and maintenance of OGA.


Asunto(s)
Conducta Adictiva/patología , Corteza Cerebral/patología , Internet , Juegos de Video/psicología , Adolescente , Biometría , Femenino , Lóbulo Frontal/patología , Giro del Cíngulo/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Corteza Prefrontal/patología , Adulto Joven
8.
Anal Cell Pathol (Amst) ; 2022: 2376288, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35757013

RESUMEN

Gliosarcoma (GSM), a histologic variant of glioblastoma (GBM), carries a poor prognosis with less than one year of median survival. Though GSM is similar with GBM in most clinical and pathological symptoms, GBM has unique molecular and histological features. However, as the rarity of GSM samples, the genetic information of this tumor is still lacking. Here, we take a comprehensive analysis of DNA copy number variations (CNV) in GBM and GSM. Whole genome sequencing was performed on 21 cases of GBM and 15 cases of GSM. CNVKIT is used for CNV calling. Our data showed that chromosomes 7, 8, 9, and 10 were the regions where CNV frequently happened in both GBM and GSM. There was a distinct CNV signal in chromosome 2 especially in GSM. The pathway enrichment of genes with CNV was suggested that the GBM and GSM shared the similar mechanism of tumor development. However, the CNV of some screened genes displayed a disparate form between GBM and GSM, such as AMP, BEND2, HDAC6, FOXP3, ZBTB33, TFE3, and VEGFD. It meant that GSM was a distinct subgroup possessing typical biomarkers. The pathways and copy number alterations detected in this study may represent key drivers in gliosarcoma oncogenesis and may provide a starting point toward targeted oncologic analysis with therapeutic potential.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Gliosarcoma , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Variaciones en el Número de Copia de ADN/genética , Genómica , Glioblastoma/genética , Glioblastoma/patología , Gliosarcoma/genética , Gliosarcoma/patología , Gliosarcoma/terapia , Humanos
9.
Neural Regen Res ; 16(12): 2453-2464, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33907034

RESUMEN

The SOCS1/JAK2/STAT3 axis is strongly associated with tumor growth and progression, and participates in cytokine secretion in many diseases. However, the effects of the SOCS1/JAK2/STAT3 axis in experimental subarachnoid hemorrhage remain to be studied. A subarachnoid hemorrhage model was established in rats by infusing autologous blood into the optic chiasm pool. Some rats were first treated with JAK2/STAT3 small interfering RNA (Si-JAK2/Si-STAT3) or overexpression plasmids of JAK2/STAT3. In the brains of subarachnoid hemorrhage model rats, the expression levels of both JAK2 and STAT3 were upregulated and the expression of SOCS1 was downregulated, reaching a peak at 48 hours after injury. Simultaneously, the interactions between JAK2 and SOCS1 were reduced. In contrast, the interactions between JAK2 and STAT3 were markedly enhanced. Si-JAK2 and Si-STAT3 treatment alleviated cortical neuronal cell apoptosis and necrosis, destruction of the blood-brain barrier, brain edema, and cognitive functional impairment after subarachnoid hemorrhage. This was accompanied by decreased phosphorylation of JAK2 and STAT3 protein, decreased total levels of JAK2 and STAT3 protein, and increased SOCS1 protein expression. However, overexpression of JAK2 and STAT3 exerted opposite effects, aggravating subarachnoid hemorrhage-induced early brain injury. Si-JAK2 and Si-STAT3 inhibited M1-type microglial conversion and the release of pro-inflammatory factors (inducible nitric oxide synthase, interleukin-1ß, and tumor necrosis factor-α) and increased the release of anti-inflammatory factors (arginase-1, interleukin-10, and interleukin-4). Furthermore, primary neurons stimulated with oxyhemoglobin were used to simulate subarachnoid hemorrhage in vitro, and the JAK2 inhibitor AG490 was used as an intervention. The in vitro results also suggested that neuronal protection is mediated by the inhibition of JAK2 and STAT3 expression. Together, our findings indicate that the SOCS1/JAK2/STAT3 axis contributes to early brain injury after subarachnoid hemorrhage both in vitro and in vivo by inducing inflammatory responses. This study was approved by the Animal Ethics Committee of Anhui Medical University and the First Affiliated Hospital of University of Science and Technology of China (approval No. LLSC-20180202) on March 1, 2018.

10.
Zhonghua Yi Xue Za Zhi ; 90(5): 305-9, 2010 Feb 02.
Artículo en Zh | MEDLINE | ID: mdl-20368050

RESUMEN

OBJECTIVE: To investigate the expressions of putative brain tumor stem cell (BTSC) marker CD133, Nestin and blood vessel endothelial cell marker CD31 in 65 cases of formalin fixed paraffin embedded gliomas. The relationship of BTSC distribution with micro-blood vessels was analyzed using morphometry. METHODS: (1) The expression levels of Nestin and CD133 proteins were detected using SABC immunohistochemical analysis. Then we calculated the percentage of CD133(+) cells, CD133(+) blood vessels, Nestin(+) cells and Nestin(+) blood vessels among 65 tumors, grade II (n = 18), grade III (n = 23) and grade IV (n = 24), according to WHO 2000 classification of nervous system tumors. (2) Double immunofluorescence staining was used to detect the co-expressions of CD133/CD31, CD133/Nestin and Nestin/CD31. Then the correlation of two different marked cells with the corresponding positive vascular endothelial cells were determined. RESULTS: CD133(+) cells and Nestin(+) cells could be observed in all glioma tissues. Furthermore they could also be observed expressing in the endothelial cells. In low-grade group, there were fewer CD133(+) blood vessels or Nestin(+) blood vessels in the regions which CD133(+)cells or Nestin(+) cells distributed compared with the high-grade group. The CD133(+)/CD31(+) and Nestin(+)/CD31(+) cells could be found co-expressed in the endothelial cells by using double immunofluorescence staining. Positive correlation was observed between the CD133(+) cells and CD133(+) blood vessels (r = 0.945, P < 0.01). It was similar to the correlation between the Nestin(+) blood vessels and Nestin(+) cells (r = 0.727, P < 0.01). CONCLUSION: In gliomas, the endothelial cells express brain tumor stem cells markers. Therefore the capillaries in gliomas may come from the differentiation of BTSCs. And the BTSCs are accumulated around the capillaries. Along with the rank of tumor grades, positive correlation is observed between CD133(+) cells or Nestin(+) cells with the corresponding blood vessels.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Células Madre Neoplásicas/metabolismo , Antígeno AC133 , Antígenos CD/metabolismo , Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/patología , Diferenciación Celular , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Glioma/irrigación sanguínea , Glioma/patología , Glicoproteínas/metabolismo , Humanos , Proteínas de Filamentos Intermediarios/metabolismo , Microcirculación , Estadificación de Neoplasias , Células Madre Neoplásicas/citología , Proteínas del Tejido Nervioso/metabolismo , Nestina , Péptidos/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo
11.
Pathol Res Pract ; 216(4): 152883, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32088087

RESUMEN

OBJECTIVE: To investigate the role and mechanisms of HAUSP (Herpesvirus Associated Ubiquitin Specific Protease) and NANOG in pathogenesis of malignant human gliomas progression. METHODS: Lentivirus-mediated HAUSP over-expression and RNAiHAUSP mediated HAUSP down-regulation were established in the glioma cells (U87 and U251 cell lines). Firstly, Real-time qPCR, western-blot (WB) and immunofluorescence staining were performed to detect mRNA levels, protein expressions and deposition of HAUSP and NANOG in the glioma cells, respectively. Then cell proliferation, invasion, apoptosis and xenograft tumor growth in nude mice were assessed by using cell counting kit-8 (CCK-8) assay, transwell assay, flow cytometry (FCM) and Hematoxylin-Eosin (HE) staining. RESULTS: We first demonstrated HAUSP was significantly increased in lentivirus- mediated HAUSP over-expression cells compared to the Control group. HAUSP over-expression could upregulate genes involved in proliferation and invasion such as NANOG. However, the mRNA of NANOG had no significant changes. Similarly, in RNAiHAUSP mediated HAUSP down-regulation group, HAUSP were significantly decreased compared to the Control group. Simultaneously, NANOG protein were decreased significantly, which decreased the proliferation and invasion, increased the apoptosis rate of glioma cells. Finally, low expression of HAUSP could suppress xenograft tumors growth in nude mice in different periods. CONCLUSION: This study revealed that HAUSP-NANOG pathway is a key target to inhibit glioma cells proliferation, and NANOG play important role in the formation and evolution of glioma cells. The regulation of HAUSP could change the biological activity of glioma cells through regulate NANOG expression.


Asunto(s)
Neoplasias Encefálicas/patología , Glioma/patología , Proteína Homeótica Nanog/metabolismo , Peptidasa Específica de Ubiquitina 7/metabolismo , Animales , Apoptosis/fisiología , Neoplasias Encefálicas/metabolismo , Proliferación Celular/fisiología , Glioma/metabolismo , Xenoinjertos , Humanos , Ratones , Ratones Desnudos
12.
World Neurosurg ; 130: e551-e557, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31254699

RESUMEN

OBJECTIVE: The purpose of the present study was to construct a nomogram for postoperative delirium (POD) after deep brain stimulation (DBS) surgery in patients with Parkinson's disease (PD). METHODS: The present study retrospectively enrolled 165 patients with PD who had undergone DBS surgery. The patients were assessed using the Confusion Assessment Method for the Intensive Care Unit and were divided into 2 groups: the delirium group and nondelirium group. The nomogram for POD after DBS surgery was constructed from the results of univariate analysis and multivariate logistic analysis of the influencing factors for POD after DBS surgery. RESULTS: Univariate analysis revealed that the preoperative length of stay and the presence of preoperative brain atrophy, preoperative pulmonary inflammation, and postoperative cerebral edema were statistically significant. The results from the nonmotor symptoms scale for PD, mini-mental state examination, PD sleep scale, and unified PD rating scale III were also statistically significant (P < 0.05). Multivariate logistic regression analysis showed that the unified PD rating scale III (odds ratio [OR], 2.284; 95% confidence interval [CI], 1.614-3.232), nonmotor symptoms scale for PD (OR, 8.191; 95% CI, 5.629-11.917), PD sleep scale (OR, 0.058; 95% CI, 0.05-0.067), preoperative length of stay (OR, 1.230; 95% CI, 1.053-1.437), and preoperative brain atrophy (OR, 3.912; 95% CI, 3.5-4.255) were independent factors that influenced the occurrence of POD after DBS surgery. A nomogram model was constructed using these indicators. The model predicted an area under the receiver operating characteristic curve after DBS surgery of 0.870 (95% CI, 0.808-0.918), sensitivity of 74.19%, and specificity of 91.54%. CONCLUSIONS: The present study has presented a reliable and useful nomogram that can accurately predict the occurrence of POD after DBS surgery in patients with PD. This tool is easy to use and could assist physicians during the therapeutic decision-making process.


Asunto(s)
Estimulación Encefálica Profunda , Delirio/etiología , Procedimientos Neuroquirúrgicos/efectos adversos , Nomogramas , Enfermedad de Parkinson/cirugía , Núcleo Subtalámico/cirugía , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
13.
Neural Regen Res ; 14(6): 1013-1024, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30762013

RESUMEN

The Wnt/Frizzled signaling pathway participates in many inflammation-linked diseases. However, the inflammatory response mediated by the Wnt/Frizzled signaling pathway in experimental subarachnoid hemorrhage has not been thoroughly investigated. Consequently, in this study, we examined the potential role of the Wnt/Frizzled signaling pathway in early brain injury in rat models of subarachnoid hemorrhage. Simultaneously, possible neuroprotective mechanisms were also investigated. Experimental subarachnoid hemorrhage rat models were induced by injecting autologous blood into the prechiasmatic cistern. Experiment 1 was designed to examine expression of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. In total, 42 adult rats were divided into sham (injection of equivalent volume of saline), 6-, 12-, 24-, 48-, 72-hour, and 1-week subarachnoid hemorrhage groups. Experiment 2 was designed to examine neuroprotective mechanisms of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. Rats were treated with recombinant human Wnt1 (rhwnt1), small interfering Wnt1 (siwnt1) RNA, and monoclonal antibody of Frizzled1 (anti-Frizzled1) at 48 hours after subarachnoid hemorrhage. Expression levels of Wnt1, Frizzled1, ß-catenin, peroxisome proliferator-activated receptor-γ, CD36, and active nuclear factor-κB were examined by western blot assay and immunofluorescence staining. Microglia type conversion and inflammatory cytokine levels in brain tissue were examined by immunofluorescence staining and enzyme-linked immunosorbent assay. Our results show that compared with the sham group, expression levels of Wnt1, Frizzled1, and ß-catenin were low and reduced to a minimum at 48 hours, gradually returning to baseline at 1 week after subarachnoid hemorrhage. rhwnt1 treatment markedly increased Wnt1 expression and alleviated subarachnoid hemorrhage-induced early brain injury (within 72 hours), including cortical cell apoptosis, brain edema, and neurobehavioral deficits, accompanied by increasing protein levels of ß-catenin, CD36, and peroxisome proliferator-activated receptor-γ and decreasing protein levels of nuclear factor-κB. Of note, rhwnt1 promoted M2-type microglia conversion and inhibited release of inflammatory cytokines (interleukin-1ß, interleukin-6, and tumor necrosis factor-α). In contrast, siwnt1 RNA and anti-Frizzled1 treatment both resulted in an opposite effect. In conclusion, the Wnt/Frizzled1 signaling pathway may participate in subarachnoid hemorrhage-induced early brain injury via inhibiting the inflammatory response, including regulating microglia type conversion and decreasing inflammatory cytokine release. The study was approved by the Animal Ethics Committee of Anhui Medical University and First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (approval No. LLSC-20180202) in May 2017.

14.
Neurosci Lett ; 692: 210-215, 2019 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-30439398

RESUMEN

Gliomas are the most common malignant primary brain tumors with poor prognosis. We attempted to explore the role of CYP17A1 in glioma progression. We demonstrated that the expression of CYP17A1 was significantly higher in the glioma tissues than the normal brain tissues, especially in malignant glioma. Moreover, the expression of CYP17A1 gene was positively correlative with glioma pathological grades. In vitro, CYP17A1 gene silence inhibited the proliferation and invasion of glioma cells and promoted the apoptosis in glioma cells. Also, the subcutaneously transplanted tumour in BALB/C-nu showed that CYP17A1 gene silence inhibited glioma growth. These results reveal that CYP17A1 plays a major role in the progress of glioma.


Asunto(s)
Neoplasias Encefálicas/genética , Glioma/genética , Esteroide 17-alfa-Hidroxilasa/genética , Animales , Apoptosis , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , Femenino , Silenciador del Gen , Vectores Genéticos , Glioma/metabolismo , Glioma/patología , Humanos , Lentivirus , Ratones Endogámicos BALB C , Clasificación del Tumor , Esteroide 17-alfa-Hidroxilasa/biosíntesis
15.
Brain Inj ; 22(9): 697-704, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18608204

RESUMEN

PRIMARY OBJECTIVE: The aim of the present study was to investigate the event-based prospective memory (EBPM) and time-based prospective memory (TBPM) in patients with lesion in prefrontal cortex (PFC) and test the hypothesis that the prefrontal cortex is involved in the prospective memory (PM) network. RESEARCH DESIGN: The performance of patients with lesion in PFC (n = 30) was compared with that of a demographically matched control group (n = 30). METHODS AND PROCEDURES: A neuropsychological battery of tests including EBPM and TBPM tasks were administered to both groups. MAIN OUTCOME AND RESULTS: The group with lesion in PFC were significantly impaired in EBPM, but insignificantly impaired in TBPM tasks. There was no difference in performance of EBPM and TBPM tasks between the patients with lesion in the left and the right PFC. CONCLUSIONS: These results suggest that the patients with lesion in PFC were impaired in EBPM, but not in TBPM, implying that EBPM and TBPM may have different neural substrates. It is possible that PFC is more selectively involved in EBPM, but less in TBPM.


Asunto(s)
Trastornos de la Memoria/etiología , Corteza Prefrontal/lesiones , Adulto , Estudios de Casos y Controles , Cognición/fisiología , Potenciales Evocados/fisiología , Femenino , Humanos , Masculino , Trastornos de la Memoria/fisiopatología , Recuerdo Mental/fisiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Reconocimiento en Psicología/fisiología , Tomografía Computarizada de Emisión
16.
Am J Transl Res ; 10(11): 3370-3384, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30662593

RESUMEN

G-protein-coupled receptor kinase-5 (GRK5) plays essential roles in multiple celluar events. However, its role in the development and progression of glioma is poorly understood. In this research, we found that GRK5 is significantly upregulated in human gliomas. For the first time, a close relationship was noted between GRK5 expression and blood vessel development in human glioma. Specifically co-expression of GRK5 and the tumor stem cell marker CD133 was observed in the cytoplasm of high grade glioma cells. The depletion of GRK5 suppressed the proliferation, migration and invasion in glioma cells, and promoted apoptosis. We next discovered that GRK5 knockdown inhibits the nuclear factor kappa B (NF-κB) pathway, thus resulting in downregulation of key downstream secretory products CCL2, IL-6 and IL-8 in glioma cell conditioned medium (CM). In addition, treatment of cells with the NF-κB stimulator PMA reversed this effect and increased the GRK5 level. Our results demonstrate an oncogenic role for GRK5 and reveal an activation of the GRK5-NF-κB pathway during the malignant progression of glioma.

17.
Neural Regen Res ; 12(7): 1145-1151, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28852398

RESUMEN

Conserved dopamine neurotrophic factor protects and rescues dopaminergic neurodegeneration induced by 6-hydroxydopamine in vivo, but its potential value in treating Parkinson's disease remains controversial. Here, we used the proteasome inhibitors lactacystin and MG132 to induce neurodegeneration of PC12 cells. Afterwards, conserved dopamine neurotrophic factor was administrated as a therapeutic factor, both pretreatment and posttreatment. Our results showed that (1) conserved dopamine neurotrophic factor enhanced lactacystin/MG132-induced cell viability and morphology, and attenuated alpha-synuclein accumulation in differentiated PC12 cells. (2) Enzyme linked immunosorbent assay showed up-regulated 26S proteasomal activity in MG132-induced PC12 cells after pre- and posttreatment with conserved dopamine neurotrophic factor. Similarly, 26S proteasome activity was upregulated in lactacystin-induced PC12 cells pretreated with conserved dopamine neurotrophic factor. (3) With regard proteolytic enzymes (specifically, glutamyl peptide hydrolase, chymotrypsin, and trypsin), glutamyl peptide hydrolase activity was up-regulated in lactacystin/MG132-administered PC12 cells after pre- and posttreatment with conserved dopamine neurotrophic factor. However, upregulation of chymotrypsin activity was only observed in MG132-administered PC12 cells pretreated with conserved dopamine neurotrophic factor. There was no change in trypsin expression. We conclude that conserved dopamine neurotrophic factor develops its neurotrophic effects by modulating proteasomal activities, and thereby protects and rescues PC12 cells against neurodegeneration.

18.
Oncotarget ; 8(50): 88163-88178, 2017 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-29152149

RESUMEN

The colorectal neoplasia differentially expressed (CRNDE) gene encodes a long non-coding RNA (lncRNA) that is the most unregulated among 129 lncRNAs differentially expressed in gliomas. In this study, we confirmed high CRNDE expression in clinical glioma specimens and observed through experiments in human glioma cell lines a novel molecular mechanism by which CRNDE may contribute to glioma pathogenesis. By inducing or silencing CRNDE expression, we detected a positive correlation between CRNDE levels and the proliferative, migratory, and invasive capacities of glioma cells, which were concomitant with a decreased apoptosis rate. Our experiments also suggest that these effects are mediated by downregulation of miR-136-5p, which correlated with the glioma WHO grade. Based on predicted CRNDE/miR-136-5p/mRNA interactions, both the mRNA and protein expression analyses suggested that miR-136-5p-mediated repression of Bcl-2 and Wnt2 underlies the pro-tumoral actions of CRNDE. We therefore propose that CRNDE functions as a competing endogenous RNA (ceRNA) that binds to and negatively regulates miR-136-5p, thereby protecting Bcl-2 and Wnt2 from miR-136-5p-mediated inhibition in glioma.

19.
Zhonghua Yi Xue Za Zhi ; 86(45): 3169-72, 2006 Dec 05.
Artículo en Zh | MEDLINE | ID: mdl-17313778

RESUMEN

OBJECTIVE: To investigate the influence of injury of prefrontal cortex on the risk-taking decision-making and to test the hypothesis that the orbitofrontal area is involved in the special network of risk-taking decision-making. METHODS: 47 patients with lesions in the prefrontal lobe, 21 in the orbitofrontal area (OBF) and 19 in the dorsolateral prefrontal cortex (DLF), and 40 healthy controls (HC group) were administered with a risk-taking task. RESULTS: The risky response rate after punishment of the HC group was 0.54 +/- 0.23, significantly fewer than before punishment (t = -3.82, P < 0.01), and the risky response rate after punishment of the DLF injury group was 0.68 +/- 0.16, significantly fewer than before punishment too (t = -2.32, P < 0.05). The risky response rate after reward of the patients with lesions in OBF areas was 0.79 +/- 0.19, significantly higher than that of the HC group (0.68 +/- 0.16, P < 0.05), and the risky response rate after punishment of the patients with lesions in OBF areas was 0.82 +/- 0.18, significantly higher than that of the HC group (0.54 +/- 0.23, P < 0.05). The risky response rates after reward and after punishment of the DLP group were 0.72 +/- 0.22 and 0.63 +/- 0.25 respectively, both not significantly different from those of the HC group (both P > 0.05). CONCLUSION: The patients with lesions in the orbitofrontal area, not in the dorsolateral prefrontal cortex, have a specific deficit in risk-taking decision-making, i.e. an inhibition effect of punishment, reduced sensitivity to punishment but increased sensitivity to reward. The orbitofrontal areas play an important role in risk-taking decision-making processes.


Asunto(s)
Encefalopatías/psicología , Núcleos Talámicos Laterales/patología , Corteza Prefrontal/patología , Asunción de Riesgos , Adaptación Psicológica , Adulto , Encefalopatías/complicaciones , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Toma de Decisiones , Femenino , Humanos , Núcleos Talámicos Laterales/fisiopatología , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Corteza Prefrontal/fisiopatología
20.
Int J Oncol ; 42(5): 1533-40, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23467648

RESUMEN

MiR-134 is a brain-enriched miRNA that plays an essential role in the development of the embryonic stem cell-orientated differentiation to central nervous system by suppression of Nanog and neural development (including neurons, cylindraxile and dendrites) and has been shown to be downregulated in oligodendrogliomas (ODG) and glioblastomas (GBM), suggesting its possible involvement in brain tumor progression. In this study, we defined the expression and function of miR-134, which we found to be downregulated in glioma samples and the glioblastoma cell line U87 by SYBR green real-time quantitative reverse transcription-PCR (real-time PCR). Early reports have characterized Nanog as a direct target of miR-134 by a dual-luciferase reporter assay in 293T cells. In our study, overexpression of miR-134 in U87 glioblastoma cells resulted in significant downregulation of Nanog mRNA levels as well as protein levels. miR-134 overexpression reduced the proliferation, invasiveness and migration capability of U87 cells while promoted apoptosis of these cells in vitro and suppressed the growth of tumor xenografts in vivo. These findings demonstrated that miR-134 deregulation is common in human gliomas. Restoration of its function inhibits cell proliferation, invasion and migration capability and promotes apoptosis, which could be partly due to its inhibitory effect on Nanog protein expression in glioblastoma cells. MiR-134 could play an important role as a tumor suppressor relying on its direct translational attenuation of Nanog.


Asunto(s)
Neoplasias Encefálicas/genética , Glioblastoma/genética , Proteínas de Homeodominio/metabolismo , MicroARNs/genética , Apoptosis/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Diferenciación Celular/genética , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Células Madre Embrionarias/metabolismo , Células Madre Embrionarias/patología , Regulación Neoplásica de la Expresión Génica , Glioblastoma/metabolismo , Glioblastoma/patología , Proteínas de Homeodominio/genética , Humanos , MicroARNs/metabolismo , Proteína Homeótica Nanog , Invasividad Neoplásica/genética , Neurogénesis/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA