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Chinese medicinal preparations play an equally important role in reducing toxicity and treating tumors. Few studies discriminate the quality markers(Q-markers) conferring different therapeutic effects of traditional Chinese medicine preparations. Therefore, we take Aidi Injection(AD) as an example to comprehensively identify the Q-markers of anti-tumor and cardioprotective effects based on the "spider web" mode. Firstly, based on the principle of measurability, the chemical components in the prescription were qualitatively analyzed, and then the components with high content and capable to be measured were quantitatively analyzed as measurable evaluation indexes. Based on the principle of stability, the effects of light and temperature on the content of each component of AD were investigated as indicators of stability. Based on the principle of compatibility, the compounds were classified according to the law of compatibility of sovereign, minister, assistant, and guide medicinal materials in the prescription. Based on the principle of efficacy, the anti-tumor and antiangiogenic activities of the Q-markers were evaluated, and their synergistic effects with doxorubicin(DOX) in inhibiting tumorigenesis and angiogenesis and lowering cardiotoxicity were evaluated as the evaluation indexes of effectiveness. The seven-dimensional spider web of "compatibility-content-stability-antitumor activity-synergistic anti-tumor activity with DOX-antiangiogenic activity-synergistic anti-angiogenic activity with DOX" and the four-dimensional spider web of "compatibility-content-stability-protective effects against DOX-induced myocardial toxicity" were established, on the basis of which the Q-markers of anti-tumor and cardioprotective effects of AD were comprehensively analyzed. The results showed that 12 components were selected as the Q-markers of AD, among which cantharidin, ginsenoside Re, ginsenoside Rb_1, astragaloside â ¡, cryptochlorogenic acid, and ginsenoside Rg_2 were the anti-tumor Q-markers of AD. Ginsenoside Rd, isofraxidin, syringin, eleutheroside E, calycosin-7-O-ß-D-glucoside, and azelaic acid were the cardioprotective Q-markers of AD. Taking into account both the anti-tumor and cardioprotective effects, these Q-markers could cover the four herbs constituting the prescription. The findings provides a scientific basis for the quality control of AD and an effective method for identifying comprehensive and reasonable Q-markers for the two effects of Chinese medicinal preparations.
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Antineoplásicos , Cardiotónicos , Medicamentos Herbarios Chinos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Animales , Cardiotónicos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Humanos , Ratones , Doxorrubicina , Masculino , Inyecciones , Combinación de MedicamentosRESUMEN
OBJECTIVE: We aimed to formulate a practical clinical treatment algorithm for Holmes tremor (HT) by reviewing currently published clinical data. MATERIALS AND METHODS: We performed a systematic review of articles discussing the management of HT published between January 1990 and December 2018. We examined data from 89 patients published across 58 studies detailing the effects of pharmacological or surgical interventions on HT severity. Clinical outcomes were measured by a continuous 1-10 ranked scale. The majority of studies addressing treatment response were case series or case reports. No randomized control studies were identified. RESULTS: Our review included 24 studies focusing on pharmacologic treatments of 25 HT patients and 34 studies focusing on the effect of deep brain stimulation (DBS) in 64 patients. In the medical intervention group, the most commonly used drugs were levetiracetam, trihexyphenidyl, and levodopa. In the surgically treated group, the thalamic ventralis intermedius nucleus (VIM) and globus pallidus internus (GPi) were the most common brain targets for neuromodulation. The two targets accounted for 57.8% and 32.8% of total cases, respectively. Overall, compared to the medically treated group, DBS provided greater tremor suppression (p = 0.025) and was more effective for the management of postural tremor in HT. Moreover, GPi DBS displayed greater benefit in the resting tremor component (p = 0.042) and overall tremor reduction (p = 0.022). CONCLUSIONS: There is a highly variable response to different medical treatments in HT without randomized clinical trials available to dictate treatment decisions. A variety of medical and surgical treatment options can be considered for the management of HT. Collaborative research between different institutions and researchers are warranted and needed to improve our understanding of the pathophysiology and management of this condition. In this review, we propose a practical treatment algorithm for HT based on currently available evidence.
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Estimulación Encefálica Profunda , Temblor , Estimulación Encefálica Profunda/efectos adversos , Globo Pálido , Humanos , Levodopa , Núcleos Talámicos , Temblor/etiologíaRESUMEN
BACKGROUND: Astrocyte and microglia activation are well-known features of temporal lobe epilepsy that may contribute to epileptogenesis. However, the mechanisms underlying glia activation are not well understood. Long non-coding RNA (lncRNA) H19 has diverse functions depending on physiological or pathological state, and its role in epilepsy is unknown. We previously demonstrated that H19 was significantly upregulated in the latent period of epilepsy and may be associated with cell proliferation and immune and inflammatory responses. We therefore speculated that H19 is involved in the hippocampal glial cell activation during epileptogenesis. METHODS: H19 was overexpressed or knocked down using an adeno-associated viral vector delivery system. A rat status epilepticus model was induced by intra-amygdala kainic acid injection. Astrocyte and microglia activation were assessed by immunofluorescence and western blot analyses. Expression of proinflammatory cytokines and components of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways were evaluated with western blotting. RESULTS: H19 overexpression induced the activation of astrocytes and microglia and the release of proinflammatory cytokines (interleukin-1ß and interleukin-6 and tumor necrosis factor-α) in the hippocampus, whereas H19 knockdown inhibited status epilepticus-induced glial cell activation. Moreover, H19 activated JAK/STAT signaling by promoting the expression of Stat3 and c-Myc, which is thought to be involved in astrocyte activation. CONCLUSIONS: LncRNA H19 contributes to hippocampal glial cell activation via modulation of the JAK/STAT pathway and could be a therapeutic tool to prevent the development of epilepsy.
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Epilepsia del Lóbulo Temporal/patología , Hipocampo/patología , Neuroglía/metabolismo , ARN Largo no Codificante/metabolismo , Transducción de Señal/fisiología , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Epilepsia del Lóbulo Temporal/inducido químicamente , Regulación de la Expresión Génica/genética , Quinasas Janus/metabolismo , Ácido Kaínico/toxicidad , Masculino , Fosfopiruvato Hidratasa/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Transducción GenéticaRESUMEN
Understanding the molecular mechanisms mediating epileptogenesis may lead to the development of preventative therapies against epilepsy. Our previous study demonstrated that the long non-coding RNA H19 contributes to epileptogenesis by aggravating status epilepticus-induced neuronal loss, glial cell activation, mossy fiber sprouting, and cognitive impairments in epileptic rats. However, the systematic functions and downstream targets of H19 associated with epileptogenesis are still unknown. In the present study, high-throughput microarray analysis was used to explore the influence of H19 on gene expression in an epileptic rat model. A large number of genes were differentially expressed at the transcriptional level when H19 was overexpressed or knocked down. Series test of cluster analysis further distinguished genes associated with H19. Function and pathway analyses demonstrated that H19 has diverse functions related to epileptogenesis, including demyelination, immune and inflammatory responses, cell apoptosis, and activation of MAPK. This study implicates H19 in a broad spectrum of epileptogenic processes, thereby providing a range of targets for further mechanistic investigations.
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Epilepsia/genética , Secuenciación de Nucleótidos de Alto Rendimiento , ARN Largo no Codificante/genética , Animales , Análisis por Conglomerados , Modelos Animales de Enfermedad , Masculino , ARN Largo no Codificante/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Chlorophyll content and distribution in plant's leaves is an important index in estimation of plant nutrition information. In the present work, chlorophyll content and distribution in tea plant's leaves were measured by hyperspectral imaging technique. First, hyperspectral image data were captured from tea plant's leaves; then seven kinds of algorithms were used to extract the characteristic parameters from hyperspectral image; finally, seven fitted models were developed using the characteristics vectors and the reference measurements of chlorophyll contents respectively. Experimental results showed that the MSAVI2 model is superior to other models, and the results of the MSAVI2 model was achieved as follows: R = 0.843 3 and RMSE = 9.918 in the calibration set; R = 0.832 3 and RMSE = 8.601 in the prediction set. Finally, the chlorophyll content of each pixel in image was estimated by the fitted model, and the distribution of chlorophyll content in the tea plant's leaf was described by pseudo-color map. This study sufficiently demonstrated that the chlorophyll content and distribution in tea leaf can be measured by hyperspectral imaging technique.
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Clorofila/análisis , Análisis Espectral/métodos , Té/química , Algoritmos , Hojas de la Planta/químicaRESUMEN
The morphological symptom of phosphorus deficiency at early stage is similar to the appearance of leaf aging process in preliminary phase, so that visual diagnostics of phosphorus deficiency in mini-cucumber plants at early stage is practically impossible. Near infrared reflectance spectra contain information about differences in compositions of leaf tissues between phosphorus-deficient plants and healthy plants. In the present paper, near infrared reflectance spectroscopy was used to provide diagnostic information on phosphorus deficiency of mini-cucumber plants grown under non-soil conditions. Near infrared spectra was collected from 90 leaves of mini-cucumber plants. Raw cucumber spectra was preprocessed by SNV and divided into 27 intervals. The top 10 principal components (PCs) were extracted as the input of BP-ANN classifiers by principal component analysis (PCA) while the values of nutrient deficient were used as the output variables of BP-ANN and three layers BP-ANN discrimination model was built. The best experiment results were based on the top 3 principal components of No. 7 interval when the spectra was divided into 27 intervals and identification rates of the ANN model are 100% in both training set and the prediction set. The overall results show that NIR spectroscopy combined with BP-ANN can be efficiently utilized for rapid and early diagnostics of phosphorus deficiency in mini-cucumber plants.
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Cucumis sativus/química , Fósforo/análisis , Espectroscopía Infrarroja Corta , Modelos Teóricos , Fósforo/deficiencia , Hojas de la Planta , Análisis de Componente PrincipalRESUMEN
INTRODUCTION: Surgical treatments are considered for essential tremor (ET) when patients do not respond to oral pharmacological therapies. These treatments mainly comprise radiofrequency (RF) thalamotomy, gamma knife radiosurgery (GKRS), deep brain stimulation (DBS), and focused ultrasound (FUS) procedures. AREAS COVERED: We reviewed the strengths and weaknesses of each procedure and clinical outcomes for 7 RF studies (n = 85), 11 GKRS (n = 477), 33 DBS (n = 1061), and 13 FUS studies (n = 368). A formal comparison was not possible given the heterogeneity in studies. Improvements were about 42%-90% RF, 10%-79% GKRS, 45%-83% DBS, 42%-83% FUS at short-term follow-up (<12 months) and were about 54%-82% RF, 11%-84% GKRS, 18%-92% DBS, and 42%-80% FUS at long-term follow-up (>12 months). EXPERT OPINION: We found DBS with inherent advantages of being an adjustable and reversible procedure as the most frequently employed surgical procedure for control of ET symptoms. FUS is a promising procedure but has limited applicability for unilateral control of symptoms. RF is invasive, and GKRS has unpredictable delayed effects. Each of these surgical modalities has advantages and limitations that need consideration when selecting a treatment for the ET patients.
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Estimulación Encefálica Profunda , Temblor Esencial/cirugía , Temblor Esencial/diagnóstico , Humanos , Radiocirugia , Tálamo/cirugía , Resultado del TratamientoRESUMEN
Tourette syndrome (TS) is a childhood-onset, chronic neuropsychiatric disorder characterized by multiple motor and vocal tics. TS poses a considerable burden on both patients and health care providers, leading to a major detriment of educational success, occupation, and interpersonal relationships. A multidisciplinary, specialist-driven management approach is required due to the complexity of TS. However, access to such specialty care is often dramatically limited by the patients' locations and the specialists' geographic clustering in large urban centers. Telemedicine uses electronic information and communication technology to provide and support health care when distance separates participants. Therefore, we conducted this mini-review to describe the latest information on telemedicine in the assessment and management of TS and discuss the potential contributions to care for TS patients with a multidisciplinary approach. We believe that telemedicine could be a revolutionary method in improving medical access to patients with TS.
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Introduction: Deep brain stimulation (DBS) is an effective therapy for resting tremor in Parkinson's disease (PD). However, quick and objective biomarkers for quantifying the efficacy of DBS intraoperatively are lacking. Therefore, we aimed to study how DBS modulates the intraoperative neuromuscular pattern of resting tremor in PD patients and to find predictive surface electromyography (sEMG) biomarkers for quantifying the intraoperative efficacy of DBS. Methods: Intraoperative sEMG of 39 PD patients with resting tremor was measured with the DBS on and off, respectively, during the intraoperative DBS testing stage. Twelve signal features (time and frequency domains) were extracted from the intraoperative sEMG data. These sEMG features were associated with the clinical outcome to evaluate the efficacy of intraoperative DBS. Also, an sEMG-based prediction model was established to predict the clinical improvement rate (IR) of resting tremor with DBS therapy. Results: A typical resting tremor with a peak frequency of 4.93 ± 0.98 Hz (mean ± SD) was measured. Compared to the baseline, DBS modulated significant neuromuscular pattern changes in most features except for the peak frequency, by decreasing the motor unit firing rate, amplitude, or power and by changing the regularity pattern. Three sEMG features were detected with significant associations with the clinical improvement rate (IR) of the tremor scale: peak frequency power (R = 0.37, p = 0.03), weighted root mean square (R = 0.42, p = 0.01), and modified mean amplitude power (R = 0.48, p = 0.003). These were adopted to train a Gaussian process regression model with a leave-one-out cross-validation procedure. The prediction values from the trained sEMG prediction model (1,000 permutations, p = 0.003) showed a good correlation (r = 0.47, p = 0.0043) with the true IR of the tremor scale. Conclusion: DBS acutely modulated the intraoperative resting tremor, mainly by suppressing the amplitude and motor unit firing rate and by changing the regularity pattern, but not by modifying the frequency pattern. Three features showed strong robustness and could be used as quick intraoperative biomarkers to quantify and predict the efficacy of DBS in PD patients with resting tremor.
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OBJECTIVE: To compare the efficacy of subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) on reducing levodopa-induced dyskinesia (LID) in Parkinson's disease, and to explore the potential underlying mechanisms. METHODS: We retrospectively assessed clinical outcomes in 43 patients with preoperative LID who underwent DBS targeting the STN (20/43) or GPi (23/43). The primary clinical outcome was the change from baseline in the Unified Dyskinesia Rating Scale (UDysRS) and secondary outcomes included changes in the total daily levodopa equivalent dose, the drug-off Unified Parkinson Disease Rating Scale Part â ¢ at the last follow-up (median, 18 months), adverse effects, and programming settings. Correlation analysis was used to find potential associated factors that could be used to predict the efficacy of DBS for dyskinesia management. RESULTS: Compared to baseline, both the STN group and the GPi group showed significant improvement in LID with 60.73 ± 40.29% (mean ± standard deviation) and 93.78 ± 14.15% improvement, respectively, according to the UDysRS score. Furthermore, GPi-DBS provided greater clinical benefit in the improvement of dyskinesia (P < 0.05) compared to the STN. Compared to the GPi group, the levodopa equivalent dose reduction was greater in the STN group at the last follow-up (43.81% vs. 13.29%, P < 0.05). For the correlation analysis, the improvement in the UDysRS outcomes were significantly associated with a reduction in levodopa equivalent dose in the STN group (r = 0.543, P = 0.013), but not in the GPi group (r = -0.056, P = 0.801). INTERPRETATION: Both STN and GPi-DBS have a beneficial effect on LID but GPi-DBS provided greater anti-dyskinetic effects. Dyskinesia suppression for STN-DBS may depend on the reduction of levodopa equivalent dose. Unlike the STN, GPi-DBS might exert a direct and independent anti-dyskinesia effect.
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Antiparkinsonianos/efectos adversos , Estimulación Encefálica Profunda , Discinesia Inducida por Medicamentos/terapia , Globo Pálido , Levodopa/efectos adversos , Evaluación de Resultado en la Atención de Salud , Enfermedad de Parkinson/tratamiento farmacológico , Núcleo Subtalámico , Anciano , Antiparkinsonianos/administración & dosificación , Estimulación Encefálica Profunda/métodos , Discinesia Inducida por Medicamentos/etiología , Femenino , Estudios de Seguimiento , Humanos , Levodopa/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Parkinson's disease (PD) is a common movement disorder for which diagnosis mainly depends on the medical history and clinical symptoms. Exosomes are now considered an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids, and genetic material. Long noncoding (lnc) RNA in exosomes plays a critical role in many diseases, including neurodegenerative disease. AIM: To study expression differences for lncRNAs in peripheral blood exosomes of PD patients compared with healthy individuals and to look for lncRNAs that might be related to the pathogenesis of PD. MATERIALS AND METHODS: We recruited PD patients along with age- and sex-matched healthy individuals as healthy controls and evaluated levels of lncRNAs extracted from exosomes in plasma samples via next-generation sequencing and real-time quantitative PCR. Correlation analysis was conducted for the clinical characteristics of PD patients and the expression of selected lncRNAs. RESULTS: We found 15 upregulated and 24 downregulated exosomal lncRNAs in the PD group. According to bioinformatics analyses, we chose lnc-MKRN2-42:1 for further study. Interestingly, lnc-MKRN2-42:1 was positively correlated with the MDS-UPDRS III score for PD patients. CONCLUSION: Our study suggested that lnc-MKRN2-42:1 may be involved in the occurrence and development of PD.
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Exosomas/metabolismo , Perfilación de la Expresión Génica/métodos , Enfermedad de Parkinson/metabolismo , ARN Largo no Codificante/metabolismo , ARN Mensajero/metabolismo , Ribonucleoproteínas/metabolismo , Anciano , Exosomas/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/patología , ARN Largo no Codificante/genética , ARN Mensajero/genética , Ribonucleoproteínas/genéticaRESUMEN
OBJECTIVES: Glial cell activation contributes to the inflammatory response and occurrence of epilepsy. Our preliminary study demonstrated that the long non-coding RNA, H19, promotes hippocampal glial cell activation during epileptogenesis. However, the precise mechanisms underlying this effect remain unclear. MATERIALS AND METHODS: H19 and let-7b were overexpressed or silenced using an adeno-associated viral vector in vivo. Their expression in a kainic acid-induced epilepsy model was evaluated by real-time quantitative PCR, fluorescence in situ hybridization, and cytoplasmic and nuclear RNA isolation. A dual-luciferase reporter assay was used to evaluate the direct binding of let-7b to its target genes and H19. Western blot, video camera monitoring and Morris water maze were performed to confirm the role of H19 and let7b on epileptogenesis. RESULTS: H19 was increased in rat hippocampus neurons after status epilepticus, which might be due to epileptic seizure-induced hypoxia. Increased H19 aggravated the epileptic seizures, memory impairment and mossy fibre sprouting of the epileptic rats. H19 could competitively bind to let-7b to suppress its expression. Overexpression of let-7b inhibited hippocampal glial cell activation, inflammatory response and epileptic seizures by targeting Stat3. Moreover, overexpressed H19 reversed the inhibitory effect of let-7b on glial cell activation. CONCLUSIONS: LncRNA H19 could competitively bind to let-7b to promote hippocampal glial cell activation and epileptic seizures by targeting Stat3 in a rat model of temporal lobe epilepsy.
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Epilepsia del Lóbulo Temporal/genética , Hipocampo/metabolismo , MicroARNs/genética , ARN Largo no Codificante/genética , Factor de Transcripción STAT3/metabolismo , Animales , Modelos Animales de Enfermedad , Epilepsia/genética , Epilepsia/metabolismo , Epilepsia del Lóbulo Temporal/metabolismo , Genes Supresores de Tumor/fisiología , Masculino , Ratas Sprague-Dawley , Convulsiones/genética , Convulsiones/metabolismoRESUMEN
Levodopa-induced dyskinesia (LID) is a common complication of chronic dopamine replacement therapy in the treatment of Parkinson's disease (PD). Long noncoding RNAs regulate gene expression and participate in many biological processes. However, the role of long noncoding RNAs in LID is not well understood. In the present study, we examined the lncRNA transcriptome profile of a rat model of PD and LID by RNA sequence and got a subset of lncRNAs, which were gradually decreased during the development of PD and LID. We further identified a previously uncharacterized long noncoding RNA, NONRATT023402.2, and its target genes glutathione S-transferase omega (Gsto)2 and prostaglandin E receptor (Ptger)3. All of them were decreased in the PD and LID rats as shown by quantitative real-time PCR, fluorescence in situ hybridization and western blotting. Pearson's correlation analysis showed that their expression was positively correlated with the dyskinesia score of LID rats. In vitro experiments by small interfering RNA confirmed that slicing NONRATT023402 inhibited Gsto2 and Ptger3 and promoted the inflammatory response. These results demonstrate that NONRATT023402.2 may have inhibitive effects on the development of PD and LID.
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Antiparkinsonianos/efectos adversos , Discinesias/etiología , Levodopa/efectos adversos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/etiología , ARN Largo no Codificante , Transcriptoma , Animales , Antiparkinsonianos/farmacología , Biomarcadores , Biología Computacional/métodos , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Inmunohistoquímica , Levodopa/farmacología , Modelos Biológicos , Enfermedad de Parkinson/tratamiento farmacológico , RatasRESUMEN
Dielectrophoretic (DEP) droplet dispensing using dielectric-coated coplanar electrode structures provides an ideal platform for testing smart control systems for high-speed microfluidic devices. Open-loop control of DEP droplet dispensing is not sufficiently robust for precision droplet dispensing because unavoidable surface property variations of the substrates and other parameters such as liquid viscosity introduce uncertainty in the motion. Closed-loop systems employing distributed optical sensors and feedback provide flexibility, sensitivity, and reliability. In this new scheme, an array of distributed optical sensors detects fluid motion and, through a programmable control module, triggers application of AC voltage bursts of appropriate magnitude, duration, and frequency to control liquid motion and droplet formation. Reconfiguring the module connections and reprogramming the control module permits testing of a variety of control strategies.
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Electroforesis por Microchip/instrumentación , Retroalimentación , Técnicas Analíticas Microfluídicas/instrumentación , Microfluídica/instrumentación , Nanotecnología/instrumentación , Electroforesis por Microchip/métodos , Diseño de Equipo , Microquímica/instrumentación , Microquímica/métodos , Técnicas Analíticas Microfluídicas/métodos , Microfluídica/métodos , Miniaturización , Nanotecnología/métodos , Sensibilidad y Especificidad , Transductores , Grabación en VideoRESUMEN
Positron emission tomography (PET) scan with tracer [18F]-fluorodeoxy-glucose (18F-FDG) is widely used to measure the glucose metabolism in neurodegenerative disease such as Idiopathic Parkinson's disease (IPD). Previous studies using 18F-FDG PET mainly focused on the motor or non-motor symptoms but not the severity of IPD. In this study, we aimed to determine the metabolic patterns of 18F-FDG in different stages of IPD defined by Hoehn and Yahr rating scale (H-Y rating scale) and to identify regions in the brain that play critical roles in disease progression. Fifty IPD patients were included in this study. They were 29 men and 21 women (mean±SD, age 57.7±11.1 years, disease duration 4.0±3.8 years, H-Y 2.2±1.1). Twenty healthy individuals were included as normal controls. Following 18F-FDG PET scan, image analysis was performed using Statistical Parametric Mapping (SPM) and Resting-State fMRI Data Analysis Toolkit (REST). The metabolic feature of IPD and regions-of-interests (ROIs) were determined. Correlation analysis between ROIs and H-Y stage was performed. SPM analysis demonstrated a significant hypometabolic activity in bilateral putamen, caudate and anterior cingulate as well as left parietal lobe, prefrontal cortex in IPD patients. In contrast, hypermetabolism was observed in the cerebellum and vermis. There was a negative correlation (p=0.007, r=-0.412) between H-Y stage and caudate metabolic activity. Moreover, the prefrontal area also showed a negative correlation with H-Y (P=0.033, r=-0.334). Thus, the uptake of FDG in caudate and prefrontal cortex can potentially be used as a surrogate marker to evaluate the severity of IPD.
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The molecular mechanisms underlying the development of epilepsy, i.e., epileptogenesis, are due to altered expression of a series of genes. Global expression profiling of temporal lobe epilepsy is confounded by a number of factors, including the variability among animal species, animal models, and tissue sampling time-points. In this study, we pooled two microarray datasets of the most used pilocarpine and kainic acid epilepsy models from the Gene Expression Omnibus database. A total of 567 known and novel genes were commonly differentially expressed across the two models. Pathway analyses demonstrated that the dysregulated genes were involved in 46 pathways. Real-time PCR and western blot analysis confirmed the activation of extracellular matrix (ECM)/integrin signaling pathways. Moreover, targeting ECM/integrin signaling inhibits astrocyte activation and promotes neuron injury in the hippocampus of epileptic mice. This study may provide a "gene/pathway database" that with further investigation can determine the mechanisms underlining epileptogenesis and the possible targets for neuron protection in the hippocampus after status epilepticus.
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Epilepsia del Lóbulo Temporal/genética , Proteínas de la Matriz Extracelular/genética , Perfilación de la Expresión Génica , Integrinas/genética , Transducción de Señal/genética , Animales , Bases de Datos Genéticas/estadística & datos numéricos , Epilepsia del Lóbulo Temporal/inducido químicamente , Redes Reguladoras de Genes , Hipocampo/metabolismo , Humanos , Ácido Kaínico , Masculino , Metaanálisis como Asunto , Ratones , Análisis por Micromatrices , Pilocarpina , RatasRESUMEN
OBJECTIVE: We aimed to study the networks' mechanism of metabolic covariance networks in mesial temporal lobe epilepsy (mTLE), through examining the brain value of fluorine-18-fluorodeoxyglucose positron emission tomography (18 F-FDG-PET). METHODS: 18 F-FDG-PET images from 16 patients with mTLE were analyzed using local and global metabolic covariance network (MCN) approaches, including whole metabolic pattern analysis (WMPA), hippocampus-based (h-) MCN, whole brain (w-) MCN, and edge-based connectivity analysis (EBCA). RESULTS: WMPA showed a typical ipsilateral hypometabolism and contralateral hypermetabolism pattern to epileptic zones in mTLE. h-MCN revealed decreased hippocampus-based synchronization in contralateral regions. w-MCN exhibited a disrupted metabolic network with globally increased small-world properties and regionally decreased nodal metrics in the ipsilateral hemisphere. Hippocampus (h)-EBCA and whole brain EBCA (w-EBCA) both detected a reduced-connectivity dominated metabolic covariant network. Moreover, the reduced interhemisphere connectivity seemingly played a major role in the aberrant epileptic topological pattern. CONCLUSION: From a metabolic point of view, we demonstrated the damaging effects with reduced contralateral intranetwork metrics properties and the compensatory effects in contralateral intranetworks with increased network properties. However, the import role of significant reduced interhemisphere connection has rarely been reported in other mTLE studies. Taken together, 18 F-FDG-PET MCN analysis provides new evidence that the mTLE is a system neurological disorder with disrupted networks.
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Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/metabolismo , Tomografía de Emisión de Positrones , Adolescente , Adulto , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/metabolismo , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/metabolismo , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Estudios Retrospectivos , Adulto JovenRESUMEN
A series of novel N'-tert-butyl- N'-substitutedbenzoyl-N-5-chloro-6-chromanecarbohydrazide derivatives were synthesized, and their larvicidal activities against Oriental armyworm were evaluated. The results of bioassays indicated that most of these title compounds exhibit higher larvicidal activities than RH-5849, and several of them somewhat lower than the commercial insecticide tebufenozide. The larvicidal activities are strongly associated with the types and patterns of substitution on the benzene, and 3,5-dimethyl, 2-nitro-4-chloro and 3-methyl derivatives are most prominent in increasing activity. Toxicity assays indicated that these derivatives could induce a premature, abnormal, and lethal larval moult.