RESUMO
The study aims to explore the effects of microRNA-206 (miR-206) targeting IGF-1 on the activation of hippocampal astrocytes in aged rats induced by sevoflurane through the PI3K/AKT/CREB signaling pathway. Wistar rats and astrocytes were divided into the normal/blank, sham/negative control (NC), sevoflurane (sevo), miR-206 mimics+sevo, miR-206 inhibitors+sevo, miR-206 NC+sevo, IGF-1 shRNA+sevo, and miR-206 inhibitors+IGF-1 shRNA+sevo groups. The Morris water maze test was exhibited to assess the cognitive functions. Glial fibrillary acidic protein (GFAP) expression was detected by immunofluorescence assay. Western blotting and RT-qPCR were used to detect the expression of miR-206, IGF-1, PI3K, AKT, CREB, pPI3K, pAKT, pCREB, cytochrome-c (Cyt-c), and caspase-3. Cell viability and apoptosis were detected by MTT assay and annexin V/PI double staining respectively. Mitochondrial transmembrane potential (MTP) were determined by flow cytometry. The IGF-1 shRNA+sevo group showed reduced miR-206 expression. Compared with the normal/blank group, the sevo, and miR-206 NC+sevo groups showed decreased miR-206 and GFAP expressions, cell viability and MTP but increased expressions of IGF-1, PI3K, AKT, CREB, pPI3K, pAKT, pCREB, Cyt-c and caspase-3, as well as cell apoptosis. Similar trends were observed in the miR-206 inhibitors+sevo group when compared with the sevo group. The study provides evidence that miR-206 alleviates the inhibition of activation of hippocampal astrocytes in aged rats induced by sevoflurane by targeting IGT-1 through suppressing the PI3K/AKT/CREB signaling pathway.
Assuntos
Astrócitos/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/genética , MicroRNAs/genética , Animais , Apoptose/genética , Astrócitos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Fator de Crescimento Insulin-Like I/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Interferente Pequeno/genética , Ratos , Ratos Wistar , Sevoflurano/administração & dosagem , Transdução de Sinais/efeitos dos fármacosRESUMO
We carried out this meta-analysis for the aim of exploring the influence of diabetes mellitus (DM) on the prognosis of patients with ischemic stroke. Relevant studies were identified using computerized databases supplemented with manual search strategies. The included studies were strictly followed the inclusion and exclusion criteria. Case-control studies which related to the influence of DM on the prognosis of patients with ischemic stroke were selected. Statistical analyses were implemented with the STATA version 12.0 statistical software. Our current meta-analysis initially retrieved 253 studies (227 in Chinese and 26 in English), 13 studies (6 in English and 7 in Chinese) were eventually incorporated in this meta-analysis. These 13 case-control studies included 8463 patients altogether (3249 patients with DM complicated with ischemic stroke and 5214 patients with ischemic stroke). The results of this meta-analysis manifested that there was a significant difference of the blood glucose level at 48 h after stroke between patients with DM complicated with ischemic stroke and patients with ischemic stroke (standard mean difference [SMD] =1.27, 95% confidence interval [CI] =0.02-2.51, P = 0.047); however, the effectiveness, fatality, and the National Institutes of Health Stroke Scale (NIHSS) score in patients with DM complicated with ischemic stroke, and patients with ischemic stroke had no significant difference (effectiveness: risk ratio [RR] = 0.88, 95% CI = 0.75-1.03, P = 0.121; fatality: RR = 1.29, 95% CI = 0.97-1.71, P = 0.081; NIHSS score: SMD = -0.14, 95% CI = -1.56-1.28, P = 0.849). The current evidence suggests that there is statistical difference of the blood glucose level at 48 h after stroke between patients with DM complicated with ischemic stroke and patients with ischemic stroke, but there is no statistical difference of prognostic indicators between patients in two groups. Thus, our study provides certain clinical value.
RESUMO
Rolipram specifically inhibits phosphodiesterase (PDE) 4, thereby preventing inactivation of the intracellular second messenger cyclic adenosine monophosphate (cAMP). Rolipram has been shown to play a neuroprotective role in some central nervous system (CNS) diseases. However, the role of PDE4 and the potential protective effect of rolipram on the pathophysiological process of intracerebral haemorrhage (ICH) are still not entirely clear. In this study, a mouse model of ICH was established by the collagenase method. Rolipram reduced brain oedema, blood-brain barrier (BBB) leakage, neuronal apoptosis and inflammatory cytokine release and improved neurological function in our mouse model of ICH. Moreover, rolipram increased the levels of cAMP and silent information regulator 1 (SIRT1) and upregulated the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, these effects of rolipram could be reversed by the SIRT1 inhibitor sirtinol. In conclusion, rolipram can play a neuroprotective role in the pathological process of ICH by activating the cAMP/AMPK/SIRT1 pathway.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Hemorragia Cerebral/metabolismo , AMP Cíclico/metabolismo , Inibidores da Fosfodiesterase 4/farmacologia , Rolipram/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Biomarcadores , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/etiologia , Modelos Animais de Doenças , Masculino , Camundongos , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Inibidores da Fosfodiesterase 4/uso terapêutico , Rolipram/uso terapêuticoRESUMO
INTRODUCTION: This study aims to compare the value of acute physiologic and chronic health evaluation scoring systems (APACHE II and APACHE III) among patients with acute cerebral infarction. METHODS: The APACHE II and APACHE III scores were determined in 399 patients with acute cerebral infarction within 24 h of admission in order to investigate their predictive value for prognosis in acute cerebral infarction. The area under the ROC curve was used to measure the ability of two scoring systems in predicting the prognosis of patients, and the area under the curve of the two scoring systems was compared. RESULTS: The APACHE II and APACHE III scoring systems demonstrated good predictive value for prognosis in acute cerebral infarction, and the areas under the receiver operating characteristic were 0.808 and 0.818, respectively. There was no significant difference in the area under the curve between these two scoring systems. CONCLUSION: Both the APACHE II and APACHE III scoring systems had good predictive value for prognosis in acute cerebral infarction, and there was no obvious difference between these two systems. Preference was suggested for APACHE II.
Assuntos
APACHE , Infarto Cerebral/diagnóstico , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Doença Aguda , Idoso , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Estudos Prospectivos , Curva ROCRESUMO
The objective of this study was to investigate the association between serum resistin levels and acute cerebral infarction (ACI). PubMed, SpringerLink, Wiley, EBSCO, Ovid, Web of Science, Wanfang, China National Knowledge Infrastructure, and VIP databases (last updated search in October 2014) were exhaustively searched, and data from the eligible studies were extracted and analyzed to assess the association between serum resistin levels and ACI. STATA software (version 12.0, Stata Corporation, College Station, TX, USA) was utilized for data analysis. Ten studies including 1829 ACI patients and 1557 healthy controls were eligible for inclusion in the meta-analysis. Our major result revealed that ACI patients exhibited higher serum resistin levels compared with healthy controls. Asubgroup analysis based on ethnicity showed a significant association between serum resistin levels and ACI in Asians, but surprisingly not in Caucasians. The results of our meta-analysis suggest that serum resistin levels are associated with an increased risk of ACI.