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1.
World Neurosurg ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38616029

RESUMO

BACKGROUND: Surgery is effective in the treatment of epilepsy, particularly focal epilepsy. The aim of this work was to report the incidence and grade of severity of hemorrhagic complications after cranial epilepsy surgery, and investigate the risk factors. METHODS: Patients who underwent epilepsy surgery via craniotomy between October 2003 and April 2019 were retrospectively analyzed. The incidence of hemorrhagic complications occurring in a 3-month period after cranial surgery was recorded. Other outcomes included the grade of hemorrhagic severity and risk factors. RESULTS: During the inclusion period, 2026 surgical procedures were performed. Sixty-six hemorrhagic complications were recorded. The total incidence of hemorrhagic complications after cranial epilepsy surgery was 3.3%. The most common type of hemorrhagic complications was epidural hemorrhage (57.6%), followed by intraparenchymal hemorrhage (33.3%). Forty-five patients (68.2%) had grade I complications, 4(6.1%) grade II, 16(24.2%) grade III, and 1(1.5%) grade IV. The mortality due to hemorrhagic complications was 1.5% (1/66) and hemorrhagic mortality among all cranial surgery was 0.5‰ (1/2026). Left craniotomy induced a higher percentage of severe hemorrhage than the right (34.2% vs. 14.3%). Extratemporal lobe epilepsy induced a higher percentage of severe hemorrhage than other epilepsy type (34.2% vs. 14.3%). However, no statistically significant difference was observed between these two factors (p=0.067). CONCLUSIONS: Hemorrhagic complications were uncommon after open surgery for epilepsy. Most hemorrhagic complications were mild while the severe were rare. Patients with hemorrhagic complications had a good prognosis after effective treatment.

2.
Br J Neurosurg ; : 1-8, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37927066

RESUMO

BACKGROUND: Corpus callosotomy is a palliative surgery for medically refractory epilepsy. We aim to analyze the clinical features of patients with seizure freedom and failure after total corpus callosotomy for childhood-onset refractory epilepsy. METHODS: We retrospectively reviewed the clinical courses of patients with childhood-onset refractory epilepsy undergoing total corpus callosotomy between May 2009 and March 2019. Seizure outcome at the last follow-up was the primary outcome. The clinical features of patients with seizure freedom and failure after callosotomy were compared. RESULTS: Eighty patients with childhood-onset refractory epilepsy underwent total corpus callosotomy; 15 (18.8%) obtained freedom from all seizures and 19 (23.8%) had unworthwhile improvement and failure. The mean ages at seizure onset in patients with seizure freedom and failure after callosotomy were 5.7 and 5.9 years; and mean seizure durations were 9.4 and 11.5 years, respectively. Univariate analysis found epilepsy syndrome (p = 0.047), mental retardation (p = 0.007), previous medical history (p = 0.004), ≥10 seizures per day (p = 0.024), theta waves in the background electroencephalogram (p = 0.024), and acute postoperative seizure (p = 0.000) were associated with failure after callosotomy. Seizure freedom after callosotomy was more common among patients with less than 10 seizures per day. CONCLUSIONS: Total corpus callosotomy is an effective palliative procedure for childhood-onset refractory epilepsy, particularly for patients with specific clinical characteristics. Callosotomy has a high seizure-free rate in well-selected patients.

3.
Mol Biol Rep ; 50(10): 8015-8023, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37541997

RESUMO

BACKGROUND: The tumor microenvironment contains chemokines that play a crucial role in various processes, such as tumorigenesis, inflammation, and therapy resistance, in different types of cancer. CXCL5 is a significant chemokine that has been shown to promote tumor proliferation, invasion, angiogenesis, and therapy resistance when overexpressed in various types of cancer. This research aims to investigate the impact of CXCL5 on the biological functions of glioblastoma (GBM). METHODS: The TCGA GBM and GEO databases were utilized to perform transcriptome microarray analysis and oncogenic signaling pathway analysis of CXCL5 in GBM. Validation of CXCL5 expression was performed using RT-qPCR and Western Blot. The impact of CXCL5 on cell proliferation, tumorigenesis, and angiogenesis in GBM was assessed through various methods, including cell proliferation assay, cloning assay, intracranial xenograft tumor models, and tube formation assay. Clinical prognosis was evaluated in 59 samples of gliomas with varying degrees of malignancy (grades 2, 3, and 4) and the TCGA GBM database, based on CXCL5 expression levels. The activities of the JAK-STAT and NF-κB signaling pathways were detected using Western Blot. RESULTS: The expression of CXCL5 was highly enriched in GBM. Moreover, the inhibition of CXCL5 showed a significant efficacy in suppressing cellular proliferation and angiogenesis, resulting in extended survival rates in xenograft mouse models in comparison to the control group. Notably, pretreatment with dapsone exhibited a reversal of the impact of CXCL5 on the formation of colonies and tubes in GBM cells. Elevated expression of CXCL5 was correlated with poor outcomes in GBM patients. Furthermore, the overexpression of CXCL5 has been associated with the activation of JAK-STAT and NF-κB signaling pathways. CONCLUSIONS: CXCL5 plays an important role in tumorigenesis and angiogenesis, indicating the potential for novel therapies targeting CXCL5 in GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Animais , Camundongos , NF-kappa B/metabolismo , Glioblastoma/metabolismo , Transdução de Sinais , Carcinogênese/genética , Transformação Celular Neoplásica , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral , Quimiocina CXCL5/genética , Quimiocina CXCL5/metabolismo
4.
Childs Nerv Syst ; 39(11): 3281-3288, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37318613

RESUMO

OBJECTIVE: Subdural osteoma (SO) is a rarely reported benign tumor, and there is no report of SO manifested with epileptic seizures. We aim to further the understanding of SO-related epilepsy. METHODS: Here, we report a meaningful case of epilepsy secondary to SO. A systematic review of the literature about SO using the electronic database PubMed and Web of science up to December 2022 was conducted. RESULTS: A 15-year-old girl presented with epileptic seizures for 8 years. Magnetic resonance imaging revealed an irregular lesion with heterogeneous signal in the right frontal convexity. Right frontal craniotomy was performed to remove the lesion. The pathological diagnosis was SO. Histological analysis revealed that the mechanosensitive ion channels Piezo 1/2 were upregulated in the brain tissue compressed by the osteoma, compared with the levels in the osteoma-free region. Seizure freedom was obtained during the 6-month follow-up after the surgery. We identified 24 cases of SO in 23 articles. With our case, a total of 25 cases with 32 SOs was included. Of 25 cases, 24 are adults, and 1 is a child. Seizure has been reported only in our case. Frontal osteoma was found in 76% of the patients. Symptoms were cured in 56% of the patients after surgery. CONCLUSION: Surgery is a safe and effective approach to the treatment of symptomatic osteoma. Mechanical compression on cerebral cortex may be a predisposing factor of the epileptogenesis caused by the SO.


Assuntos
Epilepsia , Osteoma , Adulto , Criança , Feminino , Humanos , Adolescente , Epilepsia/cirurgia , Epilepsia/complicações , Imageamento por Ressonância Magnética/métodos , Córtex Cerebral/patologia , Convulsões/complicações , Osteoma/diagnóstico , Osteoma/patologia , Osteoma/cirurgia
5.
Neurosurg Rev ; 46(1): 89, 2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37071225

RESUMO

The predictors of seizure outcomes after resective surgery for focal epilepsy, for an update on the features of good and poor outcomes, are investigated. A retrospective study of patients with focal epilepsy undergoing resective surgery from March 2011 to April 2019 was performed. There were 3 groups according to the seizure outcomes: seizure freedom, seizure improvement, and no improvement. Predictors of seizure outcomes were identified by multivariate logistic regression analysis. Of all 833 patients, 561 (67.3%) patients remained seizure-free at the last follow-up, 203 (24.4%) patients had seizure improvement, and 69 (8.3%) had no improvement. The mean follow-up duration was 5.2 years (range: 2.7 to 9.6). Predictors of better outcomes included epilepsy duration < 5 years, localized discharge, no. of antiepileptic drugs at surgery < 3, and temporal lobe resection. However, predictors of worse outcomes included intracranial hemorrhage in infancy, interictal abnormal discharge, intracranial electrode monitoring, and acute postoperative seizure. Our study suggests that resective surgery for focal epilepsy has satisfactory outcomes. Short epilepsy duration, localized discharge, and temporal lobe resection are positive predictors of seizure freedom. Patients with these predictors are intensively recommended for surgery.


Assuntos
Epilepsias Parciais , Epilepsia , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Epilepsias Parciais/cirurgia , Convulsões/cirurgia , Epilepsia/cirurgia , Análise Multivariada , Eletroencefalografia
6.
Aging (Albany NY) ; 15(6): 2347-2357, 2023 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-36996494

RESUMO

Accumulating evidence has demonstrated that ALDH1A3 is closely associated with development, progression, radioresistance and prognosis in a variety of cancers. However, the upstream miRNA that plays in the ALDH1A3 signaling pathways in regulating the radioresistance of glioma remains unclear. In this study, ALDH1A3 was enriched in high-grade glioma and was determined to be essential for radioresistance in GBM cell lines. Moreover, miR-320b was identified as an upstream miRNA that interacts with ALDH1A3. Low expression of miR-320b was associated with poor prognosis and radioresistance in glioma. In addition, overexpression of miR-320b counteracted the effects of ALDH1A3 on GBM cell proliferation, apoptosis and radioresistance when exposed to X-ray irradiation. Collectively, miR-320b may serve as a novel therapeutic target for glioma patients.


Assuntos
Glioma , MicroRNAs , Humanos , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Glioma/genética , Glioma/radioterapia , Apoptose/genética , Prognóstico , Linhagem Celular Tumoral , Proliferação de Células/genética
7.
Oper Neurosurg (Hagerstown) ; 24(1): 111-118, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36331213

RESUMO

BACKGROUND: Anterior temporal lobectomy is the most effective treatment for intractable temporal lobe epilepsy (TLE). However, patients are reluctant to choose this surgery for fear of risks after large frontotemporal craniotomy, and epileptologists likewise have a cautious attitude because of surgical trauma. Functional anterior temporal lobectomy (FATL) is a minimally invasive surgery procedure for addressing the above concerns. OBJECTIVE: To report preliminary data on this procedure and its safety and efficacy for treating TLE. METHODS: This consecutive case series study was conducted between October 2020 and September 2021. Patients with TLE underwent FATL by minicraniotomy with a diameter of 3 cm. Surgery duration, postoperative complications, and seizure control are described herein. Seizure outcomes were classified using Engel classifications. RESULTS: A total of 25 patients undergoing FATL for TLE were enrolled. The median epilepsy duration was 8 years. The median surgery duration was 165 min. The median blood loss was 100 mL. The median postoperative hospital stay was 8 days. No deaths occurred after surgery. Only 1 patient presented with a cerebrospinal fluid disorder that was successfully treated using a ventriculoperitoneal shunt. At the last follow-up, 23 patients (92%) were seizure-free (Engel-Ia), 1 patient remained substantially improved (Engel-II), and 1 patient obtained worthwhile seizure reduction (Engel-III). CONCLUSION: Our pilot study suggests that FATL is a viable surgical therapy for TLE. This method has the advantages of minimal invasiveness and high seizure-free rate. A controlled trial is warranted to verify the efficacy and safety of FATL comparing with anterior temporal lobectomy.


Assuntos
Lobectomia Temporal Anterior , Epilepsia do Lobo Temporal , Humanos , Lobectomia Temporal Anterior/métodos , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/complicações , Projetos Piloto , Convulsões/cirurgia , Resultado do Tratamento
8.
Front Oncol ; 12: 729002, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646656

RESUMO

Background: Lower-grade gliomas (LGGs) are characterized by remarkable genetic heterogeneity and different clinical outcomes. Classification of LGGs is improved by the development of molecular stratification markers including IDH mutation and 1p/19q chromosomal integrity, which are used as a hallmark of survival and therapy sensitivity of LGG patients. However, the reproducibility and sensitivity of the current classification remain ambiguous. This study aimed to construct more accurate risk-stratification approaches. Methods: According to bioinformatics, the sequencing profiles of methylation and transcription and imaging data derived from LGG patients were analyzed and developed predictable risk score and radiomics score. Moreover, the performance of predictable models was further validated. Results: In this study, we determined a cluster of 6 genes that were correlated with IDH mutation/1p19q co-deletion status. Risk score model was calculated based on 6 genes and showed gratifying sensitivity and specificity for survival prediction and therapy response of LGG patients. Furthermore, a radiomics risk score model was established to noninvasively assist judgment of risk score in pre-surgery. Taken together, a predictable nomogram that combined transcriptional signatures and clinical characteristics was established and validated to be preferable to the histopathological classification. Our novel multi-omics nomograms showed a satisfying performance. To establish a user-friendly application, the nomogram was further developed into a web-based platform: https://drw576223193.shinyapps.io/Nomo/, which could be used as a supporting method in addition to the current histopathological-based classification of gliomas. Conclusions: Our novel multi-omics nomograms showed the satisfying performance of LGG patients and assisted clinicians to draw up individualized clinical management.

9.
Appl Biochem Biotechnol ; 194(8): 3494-3506, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35377127

RESUMO

Accumulating evidence indicates Ribosomal protein 34 (RPL34) promotes tumor malignance and its expression is associated with poor prognosis in multiple cancer cells. However, the physiological role and biological mechanism of RPL34 in glioblastoma (GBM) remain unclear. Hence, this study aimed to investigate the expression and the role of RPL34 in GBM. A total of 59 glioma samples and 12 normal brains for epilepsy surgery were used to determine the underlying mechanisms and the biological behaviors of RPL34 in GBM. In this study, we identified that RPL34 expression was significantly (p < 0.05) enriched in GBM tumors compared with low-grade glioma and normal brain, and its expression was associated with poor survival. Additionally, RPL34 was functionally required for tumor proliferation in vitro. Mechanically, inhibition of RPL34 induced glioma cell apoptosis by activation of Bad/Caspase7/PARP signaling pathway. The RPL34 promotes cell survival in GBM and could be a potential therapeutic target for GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Proteína Ribossômica L3 , Apoptose , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioma/metabolismo , Humanos , Proteína Ribossômica L3/biossíntese , Proteína Ribossômica L3/genética , Proteína Ribossômica L3/metabolismo , Proteínas Ribossômicas/genética
10.
Clin Neurol Neurosurg ; 212: 107034, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34863054

RESUMO

PURPOSE: The purpose of this study was to demonstrate the prognostic value of afterdischarges(ADs) on surgical outcome by comparing the disparate properties in epilepsy patients with different surgical outcomes METHODS: 27 lesional epilepsy patients were retrospectively analyzed. The brain region covered by subdural electrodes in each patient was dichotomized into the area of the brain lobe(s) where the MRI lesion is located (region ML) and other brain areas (region nML). The occurrence of ADs and ADs evolving into clinical seizure, ADs threshold and ADs duration in region ML and nML were compared between seizure-free (SF) and non-seizure-free (nSF) patients. RESULTS: A total of 2535 contacts were analyzed, and the total occurrence of ADs was 18.6% (471/2535). The overall occurrence of ADs in region ML (24.8%) was significantly higher than that in region nML (10.3%) (P < 0.001). In region ML, compared with SF patients, nSF patients had a lower occurrence of ADs (19.2% vs. 31.2%, P < 0.001), a higher occurrence of ADs evolves into clinical seizure (8.7% vs. 2.4%, P = 0.006), a higher ADs threshold (12.8 ± 4.1 mA vs. 11.0 ± 3.7 mA, P < 0.001) and a shorter ADs duration (15.3 ± 14.2 s vs. 20.6 ± 17.0 s, P < 0.001). However, in region nML, there was no significant difference in properties of ADs between SF and nSF patients. CONCLUSION: Higher occurrence of ADs in region ML might predict a good outcome, whereas higher occurrence of ADs evolving into clinical seizure, higher ADs threshold and shorter ADs duration might predict an unfavorable surgical outcome. ADs might help predict surgical outcomes in epilepsy patients.


Assuntos
Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Córtex Cerebral/cirurgia , Eletrocorticografia , Epilepsia/patologia , Epilepsia/fisiopatologia , Epilepsia/cirurgia , Procedimentos Neurocirúrgicos , Avaliação de Resultados em Cuidados de Saúde , Adulto , Estimulação Elétrica , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Adulto Jovem
11.
Front Neurol ; 12: 722478, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707556

RESUMO

Purpose: To report complications after epilepsy surgery, grade the severity of complications, investigate risk factors, and develop a nomogram for risk prediction of complications. Methods: Patients with epilepsy surgery performed by a single surgeon at a single center between October 1, 2003 and April 30, 2019 were retrospectively analyzed. Study outcomes included severity grading of complications occurring during the 3-month period after surgery, risk factors, and a prediction model of these complications. Multivariable logistic regression analysis was used to calculate odds ratio and 95% confidence interval to identify risk factors. Results: In total, 2,026 surgical procedures were eligible. There were 380 patients with mild complications, 23 with moderate complications, and 82 with severe complications. Being male (odds ratio 1.29, 95% confidence interval 1.02-1.64), age at surgery (>40 years: 2.58, 1.55-4.31; ≤ 40: 2.25, 1.39-3.65; ≤ 30: 1.83, 1.18-2.84; ≤ 20: 1.71, 1.11-2.63), intracranial hemorrhage in infancy (2.28, 1.14-4.57), serial number of surgery ( ≤ 1,000: 1.41, 1.01-1.97; ≤ 1,500: 1.63, 1.18-2.25), type of surgical procedure (extratemporal resections: 2.04, 1.55-2.70; extratemporal plus temporal resections: 2.56, 1.80-3.65), surgery duration (>6 h: 1.94, 1.25-3.00; ≤ 6: 1.92, 1.39-2.65), and acute postoperative seizure (1.44, 1.06-1.97) were independent risk factors of complications. A nomogram including age at surgery, type of surgical procedure, and surgery duration was developed to predict the probability of complications. Conclusions: Although epilepsy surgery has a potential adverse effect on the patients, most complications are mild and severe complications are few. Risk factors should be considered during the perioperative period. Patients with the above risk factors should be closely monitored to identify and treat complications timely. The prediction model is very useful for surgeons to improve postoperative management.

12.
Contrast Media Mol Imaging ; 2021: 9915206, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34345227

RESUMO

This study was to explore the effect of subthalamic nucleus- (STN-) deep brain stimulation (DBS) on the neuropsychiatric function of Parkinson's disease (PD) patients using the magnetic resonance imaging (MRI) image analysis technology and the artificial intelligence (AI) algorithm. In this study, 40 PD patients admitted to our hospital from August 2018 to March 2020 were selected as the research objects, and they were divided into a control group and an observation group according to the random number table method, with 20 cases in each group. The patients in the control group were given oral treatment with levodopa tablets; and patients in the observation group were treated with STN-DBS + levodopa tablets. In patients, MRI examinations were performed before and after the treatment, and the image optimization processing algorithm under AI was adopted to process the images. The MRI imaging results of the two groups of patients were observed, analyzed, and compared before and after treatment; and the sports, cognition, and mental states of the two groups of patients were analyzed. It was believed that the MRI image before using the AI algorithm was blurry, and the image was clear after the noise reduction optimization process, which was convenient for observation. The data analysis revealed that the signal-to-noise ratio (SNR) after denoising (32.41) and structural similarity (SSIM) (0.79) had been improved. The results of the study suggested that the space occupation and bleeding symptoms of the two groups of patients were reduced after treatment, and those in the observation group were better than those of the control group; the incidences of dyskinesia and motor symptom fluctuations in the observation group were 5% and 0%, respectively, which were lower than those in the control group (35% and 25%, respectively). After treatment, the Unified Parkinson's Disease Rating Scale (UPDRS) score of the two groups of patients decreased, and it was lower in the observation group than in the control group; and the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Scale (MMSE) scores increased, and those in the observation group were higher in contrast to those in the control group (all P < 0.05). STN-DBS was beneficial to improve the clinical symptoms of patients and delay the progress of the disease, and MRI based on AI algorithms can effectively observe the changes in the neuropsychiatric function of patients, which was conducive to further clinical diagnosis and treatment.


Assuntos
Algoritmos , Estimulação Encefálica Profunda/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Transtornos Mentais/prevenção & controle , Doença de Parkinson/terapia , Núcleo Subtalâmico , Idoso , Inteligência Artificial , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Transtornos Mentais/patologia , Testes Neuropsicológicos , Resultado do Tratamento
13.
Mol Brain ; 14(1): 113, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261484

RESUMO

Clock genes not only regulate the circadian rhythm of physiological activities but also participate in the pathogenesis of many diseases. Previous studies have documented the abnormal expression of clock genes in epilepsy. However, the molecular mechanism of brain and muscle Arnt-like protein 1 (Bmal1), one of the core clock genes, in the epileptogenesis and seizures of temporal lobe epilepsy (TLE) remain unclear. We first investigated the levels of Bmal1 and other clock proteins in the hippocampus of subjects with epilepsy to define the function of Bmal1. The levels of Bmal1 were decreased during the latent and chronic phases in the experimental group compared with those in the control group. Knockout of Bmal1 in hippocampal dentate gyrus (DG) neurons of Bmal1flox/flox mice by Synapsin 1 (Syn1) promoter AAV (adeno-associated virus) lowered the threshold of seizures induced by pilocarpine administration. High-throughput sequencing analysis showed that PCDH19 (protocadherin 19), a gene associated with epilepsy, was regulated by Bmal1. PCDH19 expression was also decreased in the hippocampus of epileptic mice. Furthermore, the higher levels of Bmal1 and PCDH19 were detected in patients with no hippocampal sclerosis (no HS) than in patients with HS International League Against Epilepsy (ILAE) type I and III. Altogether, these data suggest that decreased expression of clock gene Bmal1 may participate in epileptogenesis and seizures via PCDH19 in TLE.


Assuntos
Fatores de Transcrição ARNTL/genética , Relógios Biológicos/genética , Epilepsia do Lobo Temporal/genética , Regulação da Expressão Gênica , Fatores de Transcrição ARNTL/metabolismo , Animais , Ritmo Circadiano/genética , Hipocampo/patologia , Humanos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/metabolismo , Neurônios/patologia , Pilocarpina , Protocaderinas/genética , Protocaderinas/metabolismo , Esclerose/complicações
14.
Mol Neurobiol ; 58(3): 1237-1247, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33119838

RESUMO

Mitochondrial dysfunction is closely related to the occurrence of epilepsy. Homeostasis of mitochondrial fusion and division can alleviate mitochondrial dysfunction. The trafficking kinesin protein 1 (TRAK1) is a key regulator of mitochondrial movement and regulates mitochondrial fusion-fission balance. The pathogenic variants in TRAK1 result in the severe neurodevelopmental disorders. However, the role of TRAK1 in epilepsy remains unclear. In the present study, we report that TRAK1 has a crucial function in regulation of epileptogenesis in temporal lobe epilepsy (TLE). TRAK1 expression is decreased in the patient specimens and animal model of TLE. Knockdown of TRAK1 causes an increase in mitochondrial fission factor (MFF) in vitro and the susceptibility to seizures in vivo. Exogenous overexpression of TRAK1 can rescue the dysfunction caused by TRAK1 knockdown. These findings provide new insights into the fundamental mechanisms of TRAK1 in TLE and have important implications for understanding and treating TLE via targeting mitochondrion.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/metabolismo , Dinâmica Mitocondrial , N-Acetilglucosaminiltransferases/metabolismo , Convulsões/complicações , Convulsões/metabolismo , Adolescente , Adulto , Animais , Células Cultivadas , Suscetibilidade a Doenças , Epilepsia do Lobo Temporal/patologia , Feminino , Hipocampo/patologia , Humanos , Masculino , Mitocôndrias/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Córtex Piriforme/patologia , Ratos Sprague-Dawley , Convulsões/patologia , Lobo Temporal/patologia , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Adulto Jovem
15.
IEEE Trans Neural Syst Rehabil Eng ; 28(12): 2711-2720, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33147147

RESUMO

Automatic seizure prediction promotes the development of closed-loop treatment system on intractable epilepsy. In this study, by considering the specific information exchange between EEG channels from the perspective of whole brain activities, the convolution neural network (CNN) and the directed transfer function (DTF) were merged to present a novel method for patient-specific seizure prediction. Firstly, the intracranial electroencephalogram (iEEG) signals were segmented and the information flow features of iEEG signals were calculated by using the DTF algorithm. Then, these features were reconstructed as the channel-frequency maps according to channel pairs and the frequency of information flow. Finally, these maps were fed into the CNN model and the outputs were post-processed by the moving average approach to predict the epileptic seizures. By the evaluation of cross-validation method, the proposed algorithm achieved the averaged sensitivity of 90.8%, the averaged false prediction rate of 0.08 per hour. Compared to the random predictor and other existing algorithms tested on the Freiburg EEG dataset, our proposed method achieved better performance for seizure prediction in all patients. These results demonstrated that the proposed algorithm could provide an robust seizure prediction solution by using deep learning to capture the brain network changes of iEEG signals from epileptic patients.


Assuntos
Eletrocorticografia , Epilepsia , Algoritmos , Eletroencefalografia , Epilepsia/diagnóstico , Humanos , Redes Neurais de Computação , Convulsões/diagnóstico
16.
Transl Oncol ; 13(2): 287-294, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31874375

RESUMO

Increasing evidence has indicated that PDZ binding kinase (PBK) promotes proliferation, invasion, and therapeutic resistance in a variety of cancer types. However, the physiological function and therapy-resistant role of PBK in GBM remain underexplored. In this study, PBK was identified as one of the most therapy-resistant genes with significantly elevated expression level in GBM. Moreover, the high expression level of PBK was essential for GBM tumorigenesis and radio-resistance both in vitro and in vivo. Clinically, aberrant activation of PBK was correlated with poor clinical prognosis. In addition, inhibition of PBK dramatically enhanced the efficacy of radiation therapy in GBM cells. Mechanically, PBK-dependent transcriptional regulation of CCNB2 was critical for tumorigenesis and radio-resistance in GBM cells. Collectively, PBK promotes tumorigenesis and radio-resistance in GBM and may serve as a novel therapeutic target for GBM treatment.

17.
Cell Mol Biol (Noisy-le-grand) ; 65(5): 32-37, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31304903

RESUMO

To investigate the effects of emodin on learning and memory and protein kinase C (PKC) signaling pathway in Alzheimer's disease (AD) model mice. 60 APP/PS1 double transgenic AD mice were selected as model mice at the age of 7-8 months, 36 healthy male C57BL/6 mice served as the control group. Morris water maze method and passive avoidance experiment were used to evaluate the memory ability of mice. The thiazole blue (MTT) method and the lactate dehydrogenase (LDH) cytotoxicity test kit were used to evaluate the effect of emodin on the cell viability of hippocampal neurons in HT22 mice treated with ß-amyloid peptide 1-42 (Aß1-42). The effect of emodin on PKC levels was explored using the modified Takai method and Western blotting. Behavioral test results showed that the escape latency of the mice in the model group was longer than that in the control group (P<0.05), and the escape latency was significantly shortened given a emodin prognosis. The MTT and LDH test results showed that emodin to Aß- overexpression induced the protective effect of hippocampus cells in HT22 mice. Western blot analysis showed that the phosphorylation level of PKC in mice increased significantly after emodin administration. Emodin can attenuate oxidative stress and inflammatory response in Alzheimer's model mice by activating PKC pathway, thereby improving cognitive function.


Assuntos
Doença de Alzheimer/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Emodina/farmacologia , Substâncias Protetoras/farmacologia , Proteína Quinase C/metabolismo , Transdução de Sinais/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Emodina/administração & dosagem , Emodina/uso terapêutico , Hipocampo/patologia , Inflamação/metabolismo , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Fosforilação/efeitos dos fármacos , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/uso terapêutico
18.
Clin Neurol Neurosurg ; 182: 11-16, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31054423

RESUMO

OBJECTIVE: Physical and mental status of neurosurgeons may vary with emergency status and hours of operation, which may impact the outcome of patients undergoing surgery. This study aims to clarify the influence of these parameters on outcome after surgery in glioma patients. PATIENTS AND METHODS: A total of 477 nonemergency surgery (NES) and 30 emergency surgery (ES) were enrolled in this study. Using propensity score matching (PSM) analysis, 97 pairs of procedures from NES group were generated and then classified as group M (morning procedures, 8:00 a.m-1:00 p.m) or group A (afternoon or night procedures, 1:00 p.m-8:00 p.m). 30 emergency procedures were classified into group ESa (daytime emergency surgery, 8:00 a.m-6:00 p.m) and group ESb (nighttime surgery procedures, 6:00 p.m-8:00 a.m the next day). Differences in intraoperative risk factors and postoperative complications were analyzed. RESULTS: Postoperative complications, including death within 30 days (p = 0.004), neurological function deficit (p = 0.012), systemic infection (p < 0.001) were significant higher in emergency procedures. Intraoperative risk factors including blood loss (p < 0.001), blood transfusion (p = 0.036) were also higher in emergency procedures than nonemergency procedures, although both procedures had comparable time duration (p = 0.337). By PSM analysis, patients in group M and group A were well matched and no significant difference of intraoperative risk factors and postoperative complications (all p > 0.05) were found. Furthermore, incidence of intraoperative risk factors and postoperative complications were similar in both groups ESa and ESb (all p > 0.05). CONCLUSION: Emergency glioma resection is a very important risk factors of perioperative mortality and morbidity for patients. However, hours of operation did not necessarily predict postoperative mortality or morbidity, either in emergency or nonemergency glioma resection.


Assuntos
Glioma/cirurgia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Fatores de Tempo , Adulto , Idoso , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Glioma/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Fatores de Risco
19.
Chem Biol Interact ; 305: 148-155, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-30929997

RESUMO

Accumulating evidence has documented that ataxia-telangiectasia group D complementing gene (ATDC) is aberrantly expressed in various cancers and is associated with cancer development and progression. However, little is known about the role of ATDC in glioma tumorigenesis. In this study, we aimed to explore the biological function and regulatory mechanism of ATDC in glioma. We found that ATDC expression was highly upregulated in glioma cell lines. Knockdown of ATDC significantly inhibited the growth and invasion of glioma cells. In contrast, overexpression of ATDC markedly promoted the growth and invasion of glioma cells. Moreover, our results showed that inhibition of ATDC reduced the expression levels of Dishevelled 2 (Dvl2) and ß-catenin and impeded the activation of Wnt/ß-catenin signaling, whereas overexpression of ATDC showed the opposite effect. Knockdown of Dvl2 significantly blocked the promotion effect of ATDC overexpression on activation of Wnt/ß-catenin signaling. In addition, silencing of ß-catenin partially reversed the oncogenic effect of ATDC overexpression in glioma cells. Taken together, out study reveals an oncogenic role of ATDC that drives the growth and invasion of glioma by modulating the Wnt/Dvl2/ß-catenin signaling pathway, suggesting a potential therapeutic target for treatment of glioma.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/metabolismo , Via de Sinalização Wnt , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Proteínas Desgrenhadas/metabolismo , Glioma/metabolismo , Glioma/patologia , Humanos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Regulação para Cima , beta Catenina/antagonistas & inibidores , beta Catenina/metabolismo
20.
Oncol Lett ; 11(4): 2625-2628, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27073529

RESUMO

Langerhans' cell histiocytosis (LCH) is a rare disease with a wide spectrum of clinical manifestations, varying from an isolated lesion to systemic involvement. The etiology of this disease remains to be elucidated. The present study reports a case of LCH with temporal fossa localization in an 8-year-old male patient, who had exhibited left temporal pain and headache for 1 month. Physical examination revealed slight exophthalmos and conjunctival hemorrhage in the patient's left eye, and non-contrast computed tomography imaging of the head revealed a soft tissue mass with unclear margins located in the left temporal fossa, as well as a wide bony defect. Magnetic resonance imaging revealed a heterogeneously contrast-enhanced mass near the left temporal pole, which eroded into the patient's left orbit and maxillary sinus. The lesion was totally excised and confirmed to be LCH through biopsy.

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