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1.
J Ethnopharmacol ; 264: 113206, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32750460

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Berberine is generally extracted from Rhizoma Coptidis (Coptis chinensis Franch), a traditional Chinese medicine, which can be used in the treatment of intestinal diseases, respiratory infections and cardiovascular diseases. Berberine is especially effective for the treatment of gastrointestinal disorders such as diarrhea because of the effect of heat-clearing and detoxifying in traditional Chinese medicine theory. AIM OF THE STUDY: This study aimed to examine the protective effect of berberine (BBR) on the damaged colonic epithelial barrier caused by peritoneal dialysis fluid (PDF). METHODS: The damage to intestinal epithelial barrier was examined by intraperitoneally injecting 4.25% dextrose-containing PDF in mice and establishing a long-term PD model in rats with renal failure. Then, the therapeutic potential of berberine on PD-related colonic injuries was examined. T84 colonic epithelial cells were used to test the effect of PDF and berberine in vitro. The damaging effect of PDF and the protective effect of berberine were evaluated by histology staining, histofluorescence and transmission electron microscopy. The migration of colonic epithelial cell and actin-related protein 2 (Arp2) were tested by wound healing assay and Western blot to determine the possible mechanism in vitro. RESULTS: PD administration induced intestinal epithelial barrier dysfunction in the colon, and berberine alleviated the injury by increasing the tight junction and adhesion junction protein, both in vivo and in vitro. Berberine could also improve the morphology of microvillus. In the wound healing assay, berberine exhibited the ability to promote cell migration, indicating that berberine could probably recover the function of intestinal epithelial cells when the intestinal epithelial barrier was damaged by the PDF. CONCLUSIONS: The present study demonstrates that berberine can ameliorate intestinal epithelial barrier dysfunction in the colon caused by long-term PDF through improving cell migration.

2.
J Healthc Eng ; 2020: 8854725, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029338

RESUMO

Depression is a leading cause of disability worldwide, and objective biomarkers are required for future computer-aided diagnosis. This study aims to assess the variation of frontal alpha complexity among different severity depression patients and healthy subjects, therefore to explore the depressed neuronal activity and to suggest valid biomarkers. 69 depression patients (divided into three groups according to the disease severity) and 14 healthy subjects were employed to collect 3-channel resting Electroencephalogram signals. Sample entropy and Lempel-Ziv complexity methods were employed to evaluate the Electroencephalogram complexity among different severity depression groups and healthy group. Kruskal-Wallis rank test and group t-test were performed to test the difference significance among four groups and between each two groups separately. All indexes values show that depression patients have significantly increased complexity compared to healthy subjects, and furthermore, the complexity keeps increasing as the depression deepens. Sample entropy measures exhibit superiority in distinguishing mild depression from healthy group with significant difference even between nondepressive state group and healthy group. The results confirm the altered neuronal activity influenced by depression severity and suggest sample entropy and Lempel-Ziv complexity as promising biomarkers in future depression evaluation and diagnosis.

3.
Physiol Meas ; 41(9): 095007, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021227

RESUMO

OBJECTIVE: Depression is a mental disorder that causes emotional changes and even suicide. However, there is still a lack of objective physiological data to support current clinical depression diagnosis. Accurate computer-aided diagnosis systems are becoming more and more crucial and urgent for future depression diagnosis. The purpose of this study is to analyze the electroencephalogram (EEG) regularity of depression using fuzzy measure entropy (FMEn), and thus to explore its role in the computer-aided diagnosis of depression. APPROACH: Three-channel EEG signals among 35 subjects (divided into two groups according to the severity of the disease) were recorded in this study. First, the frontal delta, theta, alpha and beta frequency bands were extracted after preprocessing, and the sample entropy (SEn) and the FMEn were calculated. Then, the difference between the two groups and the correlation between the entropy values and the Hamilton Depression Rating Scale scores were analyzed using statistical analysis. Finally, the results of FMEn were compared with those of SEn. MAIN RESULTS: A better statistically significant difference between the two groups using FMEn was revealed, with p < 0.01 in the theta and alpha bands. In terms of SEn, only SEn_Fp2 in the delta band, SEn_Fp2 in the theta band and SEn_Fp1 in the alpha band performed better, showing significant differences with p = 0.0006, p = 0.002 and p = 0.0114. SIGNIFICANCE: These findings suggest that frontal EEG signal complexity analysis with depression using FMEn might be more sensitive than that using SEn. FMEn could be considered as a promising biomarker for future clinical depression detection.

4.
Front Physiol ; 10: 359, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984033

RESUMO

Aims: This study used entropy- and cross entropy-based methods to explore the cardiorespiratory coupling of depressive patients, and thus to assess the values of those entropy methods for identifying depression patients with different disease severities. Methods: Electrocardiogram (ECG) and respiration signals from 69 depression patients were recorded simultaneously for 5 min. Patients were classified into three groups according to the Hamilton Depression Rating Scale (HDRS) scores: group Non-De (HDRS 0-7), Mid-De (HDRS 8-17), and Con-De (HDRS >17). Sample entropy (SEn), fuzzy measure entropy (FMEn) and high-frequency power (HF) were computed on the original RR interval time series and breath-to-breath interval time series. Cross sample entropy (CSEn) and cross fuzzy measure entropy (CFMEn) were computed on interval time series resampled at 2 Hz and 4 Hz, respectively. The difference among three patient groups and correlation between entropy values and HDRS scores were analyzed by statistical analysis. Surrogate data were also employed to confirm the validation of entropy measures in this study. Results: A consistent increasing trend has been found among most entropy measures from Non-De, to Mid-De, and to Con-De groups, and a significant (p < 0.05) difference in FMEn of RR intervals exists between Non-De and Mid-De or Con-De groups. Significant differences have been also found in all cross entropies, between Non-De and Con-De groups and between Mid-De and Con-De groups. Furthermore, significant correlations also exist between HDRS scores and FMEn of RR intervals (R = 0.24, p < 0.05), CSEn at 4 Hz (R = 0.26, p < 0.05) or 2 Hz (R = 0.28, p < 0.05) resampling, and CFMEn at 4 Hz (R = 0.31, p < 0.01) or 2 Hz (R = 0.30, p < 0.05) resampling. A significant difference of cardiorespiratory coupling parameters between different depression stages and significant correlations between entropy measures and depression severity both indicate central autonomic dysregulation in depression patients and reflect varying degrees of vagal modulation reduction among different depression levels. Analysis based on surrogate data confirms that the non-linear properties of the physiological signals played a major role in depression recognition. Conclusion: The current study demonstrates the potential of cardiorespiratory coupling in the auxiliary diagnosis of depression based on the entropy method.

5.
Front Physiol ; 10: 167, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873046

RESUMO

Podocytes, dynamic polarized cells wrapped around glomerular capillaries, are an essential component of the glomerular filtration barrier. BK channels consist of one of the slit diaphragm (SD) proteins in podocytes, interact with the actin cytoskeleton, and play vital roles in glomerular filtration. Mechanistic target of rapamycin (mTOR) complexes regulate expression of SD proteins, as well as cytoskeleton structure, in podocytes. However, whether mTOR complexes regulate podocyte BK channels is still unclear. Here, we investigated the mechanism of mTOR complex regulation of BK channels via real-time PCR, western blot, immunofluorescence, and patch clamping. Inhibiting mTORC1 with rapamycin or downregulating Raptor had no significant effect on BK channel mRNA and protein levels and bioactivity. However, the dual inhibitor of mTORC1 and mTORC2 AZD8055 and short hairpin RNA targeting Rictor downregulated BK channel mRNA and protein levels and bioactivity. In addition, MK2206, GF109203X, and GSK650394, which are inhibitors of Akt, PKCα, and SGK1, respectively, were employed to test the downstream signaling pathway of mTORC2. MK2206 and GF109203X had no effect on BK channel protein levels. MK2206 caused an obvious decrease in the current density of the BK channels. Moreover, GSK650394 downregulated the BK channel protein and mRNA levels. These results indicate mTORC2 not only regulates the distribution of BK channels through Akt, but also modulates BK channel protein expression via SGK1 in podocytes.

6.
Mol Biosyst ; 13(3): 577-584, 2017 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-28145541

RESUMO

Essential genes are required for the viability of an organism. Accurate and rapid identification of new essential genes is of substantial theoretical interest to synthetic biology and has practical applications in biomedicine. Fractals provide facilitated access to genetic structure analysis on a different scale. In this study, machine learning-based methods using solely fractal features are presented and the problem of predicting essential genes in bacterial genomes is evaluated. Six fractal features were investigated to learn the parameters of five supervised classification methods for the binary classification task. The optimal parameters of these classifiers are determined via grid-based searching technique. All the currently available identified genes from the database of essential genes were utilized to build the classifiers. The fractal features were proven to be more robust and powerful in the prediction performance. In a statistical sense, the ELM method shows superiority in predicting the essential genes. Non-parameter tests of the average AUC and ACC showed that the fractal feature is much better than other five compared features sets. Our approach is promising and convenient to identify new bacterial essential genes.


Assuntos
Fractais , Genes Essenciais , Aprendizado de Máquina , Bactérias/genética , Bases de Dados de Ácidos Nucleicos , Genes Bacterianos , Genômica/métodos , Humanos , Dinâmica não Linear , Curva ROC
7.
Technol Health Care ; 25(3): 447-456, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27911349

RESUMO

Recent studies have indicated that physiological parameters change with different emotion states. This study aimed to quantify the changes of vascular function at different emotion and sub-emotion states. Twenty young subjects were studied with their finger photoplethysmographic (PPG) pulses recorded at three distinct emotion states: natural (1 minute), happiness and sadness (10 minutes for each). Within the period of happiness and sadness emotion states, two sub-emotion states (calmness and outburst) were identified with the synchronously recorded videos. Reflection index (RI) and stiffness index (SI), two widely used indices of vascular function, were derived from the PPG pulses to quantify their differences between three emotion states, as well as between two sub-emotion states. The results showed that, when compared with the natural emotion, RI and SI decreased in both happiness and sadness emotions. The decreases in RI were significant for both happiness and sadness emotions (both P< 0.01), but the decreases in SI was only significant for sadness emotion (P< 0.01). Moreover, for comparing happiness and sadness emotions, there was significant difference in RI (P< 0.01), but not in SI (P= 0.9). In addition, significant larger RI values were observed with the outburst sub-emotion in comparison with the calmness one for both happiness and sadness emotions (both P< 0.01) whereas significant larger SI values were observed with the outburst sub-emotion only in sadness emotion (P< 0.05). Moreover, gender factor hardly influence the RI and SI results for all three emotion measurements. This pilot study confirmed that vascular function changes with diffenrt emotion states could be quantified by the simple PPG measurement.


Assuntos
Vasos Sanguíneos/fisiologia , Emoções/fisiologia , Depressão/fisiopatologia , Feminino , Felicidade , Humanos , Masculino , Fotopletismografia , Projetos Piloto , Pulso Arterial , Rigidez Vascular/fisiologia , Gravação em Vídeo , Adulto Jovem
8.
Mol Cell Endocrinol ; 389(1-2): 92-8, 2014 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-24835924

RESUMO

G-protein-coupled estrogen receptor-30 (GPR30), also known as G-protein estrogen receptor-1 (GPER1), is a putative extranuclear estrogen receptor whose precise functions in the brain are poorly understood. Studies using exogenous administration of the GPR30 agonist, G1 suggests that GPR30 may have a neuroprotective role in cerebral ischemia. However, the physiological role of GPR30 in mediating estrogen (E2)-induced neuroprotection in cerebral ischemia remains unclear. Also unclear is whether GPR30 has a role in mediating rapid signaling by E2 after cerebral ischemia, which is thought to underlie its neuroprotective actions. To address these deficits in our knowledge, the current study examined the effect of antisense oligonucleotide (AS) knockdown of GPR30 in the hippocampal CA1 region upon E2-BSA-induced neuroprotection and rapid kinase signaling in a rat model of global cerebral ischemia (GCI). Immunohistochemistry demonstrated that GPR30 is strongly expressed in the hippocampal CA1 region and dentate gyrus, with less expression in the CA3 region. E2-BSA exerted robust neuroprotection of hippocampal CA1 neurons against GCI, an effect abrogated by AS knockdown of GPR30. Missense control oligonucleotides had no effect upon E2-BSA-induced neuroprotection, indicating specificity of the effect. The GPR30 agonist, G1 also exerted significant neuroprotection against GCI. E2-BSA and G1 also rapidly enhanced activation of the prosurvival kinases, Akt and ERK, while decreasing proapototic JNK activation. Importantly, AS knockdown of GPR30 markedly attenuated these rapid kinase signaling effects of E2-BSA. As a whole, the studies provide evidence of an important role of GPR30 in mediating the rapid signaling and neuroprotective actions of E2 in the hippocampus.

9.
Mol Cell Endocrinol ; 387(1-2): 52-8, 2014 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-24594140

RESUMO

G-protein-coupled estrogen receptor-30 (GPR30), also known as G-protein estrogen receptor-1 (GPER1), is a putative extranuclear estrogen receptor whose precise functions in the brain are poorly understood. Studies using exogenous administration of the GPR30 agonist, G1 suggests that GPR30 may have a neuroprotective role in cerebral ischemia. However, the physiological role of GPR30 in mediating estrogen (E2)-induced neuroprotection in cerebral ischemia remains unclear. Also unclear is whether GPR30 has a role in mediating rapid signaling by E2 after cerebral ischemia, which is thought to underlie its neuroprotective actions. To address these deficits in our knowledge, the current study examined the effect of antisense oligonucleotide (AS) knockdown of GPR30 in the hippocampal CA1 region upon E2-BSA-induced neuroprotection and rapid kinase signaling in a rat model of global cerebral ischemia (GCI). Immunohistochemistry demonstrated that GPR30 is strongly expressed in the hippocampal CA1 region and dentate gyrus, with less expression in the CA3 region. E2-BSA exerted robust neuroprotection of hippocampal CA1 neurons against GCI, an effect abrogated by AS knockdown of GPR30. Missense control oligonucleotides had no effect upon E2-BSA-induced neuroprotection, indicating specificity of the effect. The GPR30 agonist, G1 also exerted significant neuroprotection against GCI. E2-BSA and G1 also rapidly enhanced activation of the prosurvival kinases, Akt and ERK, while decreasing proapototic JNK activation. Importantly, AS knockdown of GPR30 markedly attenuated these rapid kinase signaling effects of E2-BSA. As a whole, the studies provide evidence of an important role of GPR30 in mediating the rapid signaling and neuroprotective actions of E2 in the hippocampus.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Estradiol/farmacologia , Estrogênios/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Soroalbumina Bovina/farmacologia , Animais , Região CA1 Hipocampal/metabolismo , Região CA3 Hipocampal/metabolismo , Giro Denteado/metabolismo , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/biossíntese , Feminino , Técnicas de Silenciamento de Genes , Proteínas Quinases JNK Ativadas por Mitógeno/biossíntese , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas c-akt/biossíntese , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas-G/agonistas , Receptores Acoplados a Proteínas-G/genética , Transdução de Sinais
10.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 30(1): 67-70, 79, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23488140

RESUMO

In modern society, metabolic syndrome (MS) occurs in a state in which many diseases gather in the human body and can directly lead to cardiovascular diseases and even to death. MS generates slowly, and the early intervention, the basis of which is the evaluation of MS, can effectively alleviate the diseases. This paper presents an MS fuzzy comprehensive evaluation method based on principal component analysis (PCA). The method firstly deals with the historical data that impact the indexes of MS to obtain the weight of each index by using PCA. Then it evaluates each index to get the human health score by using fuzzy comprehensive evaluation method, and therefore it provides objective basis for the early effective intervention. Finally we verified the feasibility and effectiveness of the method using demonstration and simulation.


Assuntos
Algoritmos , Lógica Fuzzy , Síndrome Metabólica/diagnóstico , Análise de Componente Principal/métodos , Humanos
11.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 30(5): 976-81, 2013 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-24459955

RESUMO

To treat the problem of identification performance and the complexity of the algorithm, we proposed a piecewise linear representation and dynamic time warping (PLR-DTW) method for ECG biometric identification. Firstly we detected R peaks to get the heartbeats after denoising preprocessing. Then we used the PLR method to keep important information of an ECG signal segment while reducing the data dimension at the same time. The improved DTW method was used for similarity measurements between the test data and the templates. The performance evaluation was carried out on the two ECG databases: PTB and MIT-BIH. The analystic results showed that compared to the discrete wavelet transform method, the proposed PLR-DTW method achieved a higher accuracy rate which is nearly 8% of rising, and saved about 30% operation time, and this demonstrated that the proposed method could provide a better performance.


Assuntos
Algoritmos , Identificação Biométrica/métodos , Eletrocardiografia/métodos , Sistemas de Identificação de Pacientes , Reconhecimento Fisiológico de Modelo , Humanos
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 14(3): 161-4, 2012 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-22433398

RESUMO

Maple syrup urine disease is a common amino acids metabolic disease. In most patients, onset occurs in the neonatal period and infancy. In this study, the case of a school boy with acute encephalopathy due to late-onset maple syrup urine disease is summarized. The boy (8.5 years) was admitted because of acute encephalopathy after suffering from infection for two days at the age of eight and a half years. Metabolic acidosis, hyperuricemia and decreased protein level in cerebrospinal fluid were found by general laboratory tests. Magnetic resonance imaging of the brain revealed signal intensity abnormalities in the bilateral cerebellum dentate nucleus, brainstem, thalamus, putamen, caudate nucleus and cortex of the cerebral hemispheres. On T1WI and T2WI scanning, hyperintensive signal was found. Blood leucine and valine were significantly elevated. Urinary 2-hydroxy isovaleric acid, 3-hydroxybutyric acid, 2-keto isovaleric acid, and 2-keto acid also increased. Both the blood amino acid and urine organic acid profiles led to the diagnosis of maple syrup urine disease. In the acute period, the patient was treated with a large dose of vitamin B1, glucose, L-carnitine and a protein-restrict diet. The patient's condition improved significantly after five days of treatment, and he recovered completely two days later. Afterwards, treatment with vitamin B1, L-carnitine and a protein-restrict diet (1 g/kg/day) was continued. One and a half months later, blood amino acids and urine organic acids returned to normal. Magnetic resonance imaging of the brain also indicated a great improvement. It was concluded that inborn metabolic disease should be considered in the patients with an onset similar to acute encephalopathy. Early diagnosis and proper treatment can prevent brain damage and improve prognosis.


Assuntos
Encefalopatias/etiologia , Doença da Urina de Xarope de Bordo/complicações , Doença Aguda , Criança , Humanos , Imagem por Ressonância Magnética , Masculino , Doença da Urina de Xarope de Bordo/diagnóstico , Doença da Urina de Xarope de Bordo/terapia
13.
Conf Proc IEEE Eng Med Biol Soc ; 2011: 5248-51, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22255521

RESUMO

There has been a surge of research on electrocardiogram (ECG) signal based biometric for person identification. Though most of the existing studies claimed that ECG signal is unique to an individual and can be a viable biometric, one of the main difficulties for real-world applications of ECG biometric is the accuracy performance. To address this problem, this study proposes a PLR-DTW method for ECG biometric, where the Piecewise Linear Representation (PLR) is used to keep important information of an ECG signal segment while reduce the data dimension at the same time if necessary, and the Dynamic Time Warping (DTW) is used for similarity measures between two signal segments. The performance evaluation was carried out on three ECG databases, and the existing method using wavelet coefficients, which was proved to have good accuracy performance, was selected for comparison. The analysis results show that the PLR-DTW method achieves an accuracy rate of 100% for identification, while the one using wavelet coefficients achieved only around 93%.


Assuntos
Algoritmos , Biometria/métodos , Eletrocardiografia/métodos , Frequência Cardíaca/fisiologia , Sistemas de Identificação de Pacientes , Reconhecimento Automatizado de Padrão/métodos , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Análise de Ondaletas
14.
PLoS One ; 5(9): e12606, 2010 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-20830300

RESUMO

BACKGROUND: Recent work by our laboratory and others has implicated NADPH oxidase as having an important role in reactive oxygen species (ROS) generation and neuronal damage following cerebral ischemia, although the mechanisms controlling NADPH oxidase in the brain remain poorly understood. The purpose of the current study was to examine the regulatory and functional role of the Rho GTPase, Rac1 in NADPH oxidase activation, ROS generation and neuronal cell death/cognitive dysfunction following global cerebral ischemia in the male rat. METHODOLOGY/PRINCIPAL FINDINGS: Our studies revealed that NADPH oxidase activity and superoxide (O(2)(-)) production in the hippocampal CA1 region increased rapidly after cerebral ischemia to reach a peak at 3 h post-reperfusion, followed by a fall in levels by 24 h post-reperfusion. Administration of a Rac GTPase inhibitor (NSC23766) 15 min before cerebral ischemia significantly attenuated NADPH oxidase activation and O(2)(-) production at 3 h after stroke as compared to vehicle-treated controls. NSC23766 also attenuated "in situ" O(2)(-) production in the hippocampus after ischemia/reperfusion, as determined by fluorescent oxidized hydroethidine staining. Oxidative stress damage in the hippocampal CA1 after ischemia/reperfusion was also significantly attenuated by NSC23766 treatment, as evidenced by a marked attenuation of immunostaining for the oxidative stress damage markers, 4-HNE, 8-OHdG and H2AX at 24 h in the hippocampal CA1 region following cerebral ischemia. In addition, Morris Water maze testing revealed that Rac GTPase inhibition after ischemic injury significantly improved hippocampal-dependent memory and cognitive spatial abilities at 7-9 d post reperfusion as compared to vehicle-treated animals. CONCLUSIONS/SIGNIFICANCE: The results of the study suggest that Rac1 GTPase has a critical role in mediating ischemia/reperfusion injury-induced NADPH oxidase activation, ROS generation and oxidative stress in the hippocampal CA1 region of the rat, and thus contributes significantly to neuronal degeneration and cognitive dysfunction following cerebral ischemia.


Assuntos
Isquemia Encefálica/enzimologia , Isquemia Encefálica/psicologia , Cognição , NADPH Oxidases/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Isquemia Encefálica/metabolismo , Modelos Animais de Doenças , Ativação Enzimática , Hipocampo/enzimologia , Hipocampo/metabolismo , Humanos , Masculino , NADPH Oxidases/genética , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Proteínas rac1 de Ligação ao GTP/genética
15.
PLoS One ; 5(5): e9851, 2010 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-20479872

RESUMO

BACKGROUND: 17beta-estradiol (E2) has been implicated to exert neuroprotective effects in the brain following cerebral ischemia. Classically, E2 is thought to exert its effects via genomic signaling mediated by interaction with nuclear estrogen receptors. However, the role and contribution of extranuclear estrogen receptors (ER) is unclear and was the subject of the current study. METHODOLOGY/PRINCIPAL FINDINGS: To accomplish this goal, we employed two E2 conjugates (E2 dendrimer, EDC, and E2-BSA) that can interact with extranuclear ER and exert rapid nongenomic signaling, but lack the ability to interact with nuclear ER due to their inability to enter the nucleus. EDC or E2-BSA (10 microM) was injected icv 60 min prior to global cerebral ischemia (GCI). FITC-tagged EDC or E2-BSA revealed high uptake in the hippocampal CA1 region after icv injection, with a membrane (extranuclear) localization pattern in cells. Both EDC and E2-BSA exerted robust neuroprotection in the CA1 against GCI, and the effect was blocked by the ER antagonist, ICI182,780. EDC and E2-BSA both rapidly enhanced activation of the prosurvival kinases, ERK and Akt, while attenuating activation of the proapoptotic kinase, JNK following GCI, effects that were blocked by ICI182,780. Administration of an MEK or PI3K inhibitor blocked the neuroprotective effects of EDC and E2-BSA. Further studies showed that EDC increased p-CREB and BDNF in the CA1 region in an ERK- and Akt-dependent manner, and that cognitive outcome after GCI was preserved by EDC in an ER-dependent manner. CONCLUSIONS/SIGNIFICANCE: In conclusion, the current study demonstrates that activation of extranuclear ER results in induction of ERK-Akt-CREB-BDNF signaling in the hippocampal CA1 region, which significantly reduces ischemic neuronal injury and preserves cognitive function following GCI. The study adds to a growing literature that suggests that extranuclear ER can have important actions in the brain.


Assuntos
Núcleo Celular/metabolismo , Estrogênios/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Fármacos Neuroprotetores/farmacologia , Receptores Estrogênicos/metabolismo , Animais , Isquemia Encefálica/enzimologia , Isquemia Encefálica/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/enzimologia , Região CA1 Hipocampal/patologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Núcleo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Dendrímeros/farmacologia , Estradiol/metabolismo , Estradiol/farmacologia , Estrogênios Conjugados (USP)/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Injeções Intraventriculares , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Neurônios/patologia , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Soroalbumina Bovina/metabolismo , Soroalbumina Bovina/farmacologia
16.
Neurosci Res ; 63(3): 205-12, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19373993

RESUMO

Previous work has demonstrated that ischemic preconditioning neuroprotection is associated with inhibition of JNK pathway activation. The present study was designed to examine the hypothesis that the suppression of JNK3 activation by preconditioning is mediated by NMDA receptors and crosstalk between ERK1/2 and JNK3. Preconditioning (3 min ischemia) 2 days before global cerebral ischemia (8-min) markedly decreased neuronal degeneration in hippocampus CA1, an effect abolished by pretreatment with the NMDA receptor antagonist, MK-801. Furthermore, preconditioning abolished cerebral ischemia-induced JNK3 activation and enhanced ERK1/2 activation, an effect reversed by MK-801. Due to the inverse relationship between ERK1/2 and JNK3 activation following preconditioning, we hypothesized that ERK1/2 may regulate JNK3 activation following preconditioning. In support of this contention, pretreatment with the MEK inhibitor, PD98059 significantly attenuated preconditioning-induced ERK1/2 phosphorylation, and strongly reversed preconditioning down-regulation of JNK3 phosphorylation. This finding suggests that ERK1/2 signaling is responsible for preconditioning-induced down-regulation of JNK3 activation. Western blot analysis and immunohistochemistry further demonstrated that preconditioning, in an NMDA-dependent manner, enhanced activation of the pro-survival factors, p-CREB and Bcl-2, while attenuating activation of putative pro-death factors, p-c-Jun and Fas-L in the hippocampus CA1. As a whole, the study demonstrates that preconditioning attenuation of pro-death JNK3 in the hippocampus CA1 following global cerebral ischemia is mediated by NMDA receptor-induced crosstalk between ERK1/2 and JNK3. The ERK1/2-mediated reduction of JNK3 activation leads to enhanced pro-survival signaling (P-CREB and Bcl-2 induction) and attenuation of pro-death signaling (p-c-Jun and Fas-L), with subsequent induction of ischemic tolerance.


Assuntos
Isquemia Encefálica/prevenção & controle , Precondicionamento Isquêmico , Proteína Quinase 10 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Análise de Variância , Animais , Isquemia Encefálica/patologia , Proteína de Ligação a CREB/metabolismo , Modelos Animais de Doenças , Maleato de Dizocilpina/farmacologia , Regulação para Baixo , Ativação Enzimática , Flavonoides/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Marcação In Situ das Extremidades Cortadas/métodos , Masculino , Proteína Quinase 10 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fatores de Tempo
17.
Brain Res ; 1255: 32-41, 2009 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-19103177

RESUMO

The purpose of the present study was to investigate the role of myocyte enhancer binding factor 2C (MEF2C), a common substrate of p38 kinase and extracellular signal-regulated kinase 5 (ERK5) in the hippocampal CA1 region following cerebral ischemia preconditioning (CIP) and without CIP. In animals that did not undergo preconditioning, MEF2C was significantly activated with an early peak at 30 min of reperfusion, which was followed by a pronounced decrease of MEF2C protein levels in the late phase of reperfusion (3-5 d). Co-immunoprecipitation studies failed to show an interaction between ERK5 and MEF2C, and ERK5-antisense oligonucleotide (ERK5-AS) had no effect on MEF2C activation, suggesting that the MEF2C activation is mediated by a kinase other than ERK5. Following preconditioning (3 min ischemia), MEF2C was strongly activated during the late stage of reperfusion (6 h-5 d). Co-immunoprecipitation studies showed that the interaction of ERK5 and MEF2C significantly increased at 3 d of reperfusion, and this increase was markedly inhibited by ERK5-AS. Inhibition of the ERK5-MEF2C pathway resulted in a significant increase in the number of TUNEL-positive apoptotic cells compared with CIP groups in the hippocampal CA1 region, and abolished the neuroprotective effect induced by CIP. Taken together, these results demonstrate that ERK5-MEF2C signaling is significantly enhanced in the hippocampus CA1 following CIP, and that ERK5-MEF2C signaling plays a critical role in the mediation of the anti-apoptotic and neuroprotective actions of ischemic preconditioning.


Assuntos
Isquemia Encefálica/enzimologia , Isquemia Encefálica/prevenção & controle , Citoproteção , Hipocampo/enzimologia , Precondicionamento Isquêmico/métodos , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Fatores de Regulação Miogênica/metabolismo , Animais , Apoptose , Western Blotting , Isquemia Encefálica/patologia , Morte Celular , Hipocampo/patologia , Imuno-Histoquímica , Imunoprecipitação , Marcação In Situ das Extremidades Cortadas , Fatores de Transcrição MEF2 , Masculino , Ratos , Ratos Sprague-Dawley , Reperfusão/efeitos adversos , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais , Fatores de Tempo
18.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 25(1): 23-6, 52, 2008 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-18435249

RESUMO

How to detect the P300 component in EEG accurately and instantly is a hot problem in the research field of Brain-Computer Interface. In this paper, an algorithm based on F-score feature selection and support vector machines was introduced for P300 detection. Using F-score feature selection method, we reduced input features to overcome the shortcoming of support vector machines in terms of low detection speed, and then implemented the detection of P300 component with support vector machines, which have good classification performance. The algorithm was tested with a P300 dataset from the BCI competition 2003. The results showed that the algorithm achieved an accuracy of 100% in P300 detection within five repetitions, and the detection speed of this algorithm was 2 times higher than that of the traditional support vector machines algorithm without F-score feature selection.


Assuntos
Algoritmos , Eletroencefalografia/métodos , Potencial Evocado P300/fisiologia , Processamento de Sinais Assistido por Computador , Humanos , Reconhecimento Automatizado de Padrão/métodos , Análise de Componente Principal
20.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 16(12): 750-2, 2004 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-15585153

RESUMO

OBJECTIVE: To assess the serum level of leptin and its relationship between tumor necrosis factor, and endothelin in patients with chronic renal failure. METHODS: Serum level of leptin,tumor necrosis factor and endothelin were measured in 40 patients with chronic renal failure and 20 healthy controls by radioimmunoassay. Correlation analysis was performed between serum level of leptin and tumor necrosis factor and endothelin. RESULTS: Serum leptin in patients with chronic renal failure was significantly higher than that in healthy control subjects((19.25+/-4.89)microg/L vs. (5.57+/-1.69)microg/L, P<0.01). There was significant positive correlation between serum leptin and tumor necrosis factor and endothelin (r(TNF)=0.829, r(ET)=0.605; both P<0.01). CONCLUSION: The abnormal increased serum levels of tumor necrosis factor and endothelin are associated with hyperleptinemia in patients with chronic renal failure.


Assuntos
Endotelinas/sangue , Falência Renal Crônica/sangue , Leptina/sangue , Fatores de Necrose Tumoral/sangue , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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