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1.
Neurol Sci ; 44(1): 171-180, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36169754

RESUMO

OBJECTIVE: Our study aimed to investigate the correlations between microstructural changes of cingulum and patients with mild cognitive impairment (MCI) by diffusion kurtosis imaging (DKI) technique. METHOD: A total of 104 patients with cerebral small vessel diseases (cSVD) were retrospectively enrolled in this study. According to Montreal Cognitive Assessment Scale (MoCA) scores, these patients were divided into MCI group (n = 59) and non-MCI group (n = 45). The general clinical data was collected and analyzed. The regions of interests (ROIs) were selected for investigation in cingulum. The values of DKI parameters were measured in each ROI and compared between the two groups, the correlations between DKI parameters and MoCA scores were examined. RESULTS: Compared to non-MCI group, MCI patients had more severe white matter hyperintensities (WMHs) (P = 0.038) and lower MoCA scores (P < 0.01). MCI patients showed significantly decreased fractional anisotropy (FA), axial kurtosis (AK), mean kurtosis (MK), radial kurtosis (RK), and kurtosis fractional anisotropy (KFA) in the left cingulum in the cingulated cortex (CgC) region (all P < 0.0125). In the left CgC region, FA, AK, MK, RK, and KFA were positively correlated with MoCA scores (r = 0.348, 0.409, 0.310, 0.441, 0.422, all P < 0.001). Meanwhile, FA, AK, MK, RK, and KFA were also positively correlated with MoCA scores (r = 0.338, 0.352, 0.289, 0.380, 0.370, all P < 0.001) in the right CgC region. CONCLUSION: DKI technique could be used to explore the microstructural changes of cingulum in MCI patients and DKI-derived parameters might be feasible to evaluate MCI patients.


Assuntos
Disfunção Cognitiva , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Estudos Retrospectivos , Imagem de Tensor de Difusão/métodos , Córtex Cerebral , Disfunção Cognitiva/diagnóstico por imagem
2.
Plant Cell Environ ; 45(6): 1698-1718, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35141923

RESUMO

Aquaporins (AQPs) play important roles in plant growth, development and tolerance to environmental stresses. To understand the role of AQPs in the mangrove plant Kandelia obovata, which has the ability to acquire water from seawater, we identified 34 AQPs in the K. obovata genome and analysed their structural features. Phylogenetic analysis revealed that KoAQPs are homologous to AQPs of Populus and Arabidopsis, which are evolutionarily conserved. The key amino acid residues were used to assess water-transport ability. Analysis of cis-acting elements in the promoters indicated that KoAQPs may be stress- and hormone-responsive. Subcellular localization of KoAQPs in yeast showed most KoAQPs function in the membrane system. That transgenic yeast with increased cell volume showed that some KoAQPs have significant water-transport activity, and the substrate sensitivity assay indicates that some KoAQPs can transport H2 O2 . The transcriptome data were used to analyze the expression patterns of KoAQPs in different tissues and developing fruits of K. obovata. In addition, real-time quantitative PCR analyses combined transcriptome data showed that KoAQPs have complex responses to environmental factors, including salinity, flooding and cold. Collectively, the transport of water and solutes by KoAQPs contributed to the adaptation of K. obovata to the coastal intertidal environment.


Assuntos
Aquaporinas , Rhizophoraceae , Aquaporinas/genética , Aquaporinas/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Rhizophoraceae/metabolismo , Saccharomyces cerevisiae/metabolismo , Água/metabolismo
3.
Int J Neurosci ; : 1-6, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-35848522

RESUMO

BACKGROUND: In the COVID-19 epidemic more patients presented with persistent postural-perceptual dizziness (PPPD), but it has received little attention by the doctors in China and many patients reject psychological measurements or scales. Therefore, there is an urgent need for an objective method to diagnose and evaluate PPPD. OBJECTIVE: To investigate the effect of the COVID-19 epidemic on elderly PPPD patients and define the relationship between prefrontal alpha rhythm asymmetry (FAA) by Electroencephalography (EEG) and PPPD. METHODS: This case-control study was conducted to discuss the differences of elderly outpatients (>60 years) with PPPD during the peak period of COVID-19 in 2020 and the corresponding period in 2019, and collect the prefrontal FAA value in PPPD during COVID-19 outbreak, which were compared to its FAA in healthy control. RESULTS: Compared with the same period in 2019, the number of elderly PPPD patients during the epidemic period in 2020 increased significantly (16.4%, p = 0.000, x2 =31.802) . The left alpha wave signal power (F3) was significantly higher than the right alpha wave signal power (F4) (Z= -3.073, p = 0.002). In PPPD patients FAA were significantly lower in patients compared to control group (Z = -11.535, p = 0.000). There was a negative correlation between FAA and HAMA scores (R2 =0.906, p < 0.05) and a negative correlation between FAA and HAMD scores (R2 =0.859, p < 0.05), too. CONCLUSIONS: The increase in cases of elderly PPPD patients is most likely attributed to the mental health in older adults during the COVID-19 pandemic. Less left frontal brain activity in EEG may be related to elderly PPPD.

4.
BMC Neurol ; 21(1): 104, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33685396

RESUMO

BACKGROUND: Clopidogrel is an antiplatelet drug used in the treatment of ischemic stroke. Safety and efficacy of clopidogrel has been confirmed in CAPRIE, PRoFESS trials. However, these studies focused on patients aged less than 75 years. CYP2C19 polymorphisms resulted in individual differences in clopidogrel response. Our objective was to determine whether elderly stroke patients aged over 75 years would benefit from CYP2C19-genotype-guided strategy for the secondary prevention of stroke. METHODS: A retrospective analysis of patients aged 75 years or older with non-cardiogenic stroke who received 75 mg clopidogrel was performed. CYP2C19 genotype-guided group included noncarriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles (LoFA) and compared against the non-genotype-guided group which may carriers CYP2C19 LoFA or not. The primary endpoints were composite of stroke and myocardial infarction at 24 months' follow-up. RESULTS: Two hundred one patients were included: 99 in the genotype-guided group and 102 in the non-genotype-guided group. Kaplan-Meier(KM)analysis showed that CYP2C19 gene polymorphism was associated with the rate of the primary endpoints (P = 0.0031). The primary endpoints occurred in 13 patients (13.1%) in the genotype-guided group and in 30 patients (29.4%) in the non-genotype-guided group (hazard ratio(HR), 0.39; 95% confidence interval(CI), 0.20 to 0.75; p = 0.004). Cox regression analysis showed that CYP2C19 genotype-guided strategy was a protective factor for the primary endpoints (HR, 0.39; 95% CI:0.20 to 0.74, P = 0.004). CONCLUSION: The CYP2C19 genotype-guided strategy could reduce the occurrence of composite of stroke and myocardial infarction compared to a non-genotype-guided strategy for non-cardiogenic stroke patients aged 75 years or older who received clopidogrel.


Assuntos
Clopidogrel/uso terapêutico , Citocromo P-450 CYP2C19/genética , AVC Isquêmico/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Prevenção Secundária/métodos
5.
Mol Biol Rep ; 48(4): 3475-3484, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33904141

RESUMO

Ischemia-reperfusion frequently occurs in ischemic cerebral vascular disease, during which the inflammatory signaling plays essential roles. The aim of this study was to discover the efficacy of the antibody to a key immune cytokine IL-23 (anti-IL-23) for the therapy of cerebral ischemia-reperfusion injury. We established the cerebral ischemia-reperfusion injury model by middle cerebral artery occlusion (MCAO). Anti-IL-23 injection attenuated lesions indicated by histology study. RT-PCR and Western blot were employed to detect the mRNA and protein expression of JAK2 and STAT3 after anti-IL-23 treatment. ELISA was utilized to measure the levels of MDA (malondialdehyde) and superoxide dismutase (SOD). Moreover, curcumin and IL-6 were implicated in the endogenous intervention of IL-23 signaling in vivo. Our data demonstrated that the treatment of anti-IL-23 might transcriptionally activate the classic immune pathway in the brain. Anti-IL-23 augmented phosphorylation levels of both JAK2 and STAT3, suggesting the amplification signaling of JAK/STAT after exogenous IL-23 intervention. Anti-IL-23 reduced ROS molecules of STAT downstream in the serum and brain. It also alleviated the injury by bringing down levels of MDA and SOD in the serum. JAK2 inhibitor could abolish the effect of anti-IL-23 whereas JAK3 ameliorated the injury. The combination of anti-IL-23 and JAK3i could reduce infarct volume more effectively. In summary, this study indicated that anti-IL-23 had protective effects against cerebral ischemia-reperfusion injury by targeting the immune specific JAK2-STAT3 in JAK/STAT pathway.


Assuntos
Anticorpos/farmacologia , Interleucina-23/imunologia , Janus Quinase 2/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Animais , Encéfalo/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/prevenção & controle , Modelos Animais de Doenças , Masculino , Fármacos Neuroprotetores/farmacologia , Fosforilação , Processamento de Proteína Pós-Traducional , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo
6.
Neurosurg Rev ; 44(5): 2923-2931, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33502641

RESUMO

Restarting of antiplatelet therapy (AT) for patients with a history of intracerebral hemorrhage (ICH) is still a clinical dilemma in China. We aimed to investigate the association between low-dose AT and the long-term clinical outcome in Chinese ICH patients. A total of 312 patients with a history of ICH were retrospectively enrolled and followed. The ischemic vascular events, recurrent ICH, and all-cause death were reviewed retrospectively. We explored the predictors of ischemic vascular events and recurrent ICH from all patients using Cox proportional hazard regression model. One hundred fifty-one (48.4%) patients were treated with low-dose AT, and the median duration of follow-up was 4.0 years (interquartile range, 2.5-5 years). Compared to 30 (19.8%) of 151 participants who restarted low-dose AT had ischemic vascular events, 51 (31.7%) of 161 participants who did not receive AT showed ischemic vascular events (p=0.025). Eighteen (11.9%) of 151 participants treated with low-dose AT had recurrent ICH and 21 (13.0%) of 161 in non-AT participants (p=0.830). Cox regression analysis also showed that diabetes mellitus was an independent risk factor for ischemic vascular events (p=0.029). Uncontrolled blood pressure (BP) was independently associated with the risk for both ischemic vascular events (p=0.025) and recurrent ICH (p=0.001). Atrial fibrillation (AF) was an independent risk factor for recurrent ICH among patients with a history of ICH (p=0.018). In a Chinese population of patients with predominantly deep, mild to moderate severity ICH, restarting of low-dose AT at a median of 6.2 months was associated with a lower risk of ischemic vascular events without increased risk of recurrent ICH.


Assuntos
Inibidores da Agregação Plaquetária , Acidente Vascular Cerebral , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/epidemiologia , China/epidemiologia , Hospitais , Humanos , Estudos Retrospectivos , Fatores de Risco
7.
Mol Cell Biochem ; 448(1-2): 225-235, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29446046

RESUMO

Choroidal neovascularization (CNV) is the hallmark of late-staged wet age-related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a key component in the development and progression of wet AMD. DMBT, 6,6'-bis(2,3-dimethoxybenzoyl)-α,α-D-trehalose, had been proved that it could suppress tumor angiogenesis and metastasis by inhibiting production of VEGF. But the effects of DMBT on CNV were not known. This study was to investigate effects and mechanisms of DMBT on CNV in vitro and in vivo. Results showed that DMBT could inhibit migration and tube formation of RF/6A cells under ARPE-19 hypoxia conditioned medium. DMBT could reduce lesion area in laser-induced CNV model mice. ELISA and Western blotting assay showed that DMBT markedly inhibited secretion of VEGF in vitro and in vivo. Furthermore, DMBT restrained ROS level under hypoxia via suppressing Nrf2/HO-1 pathway. DMBT effectively suppressed hypoxia-induced the up-regulation of p-Akt, p-NF-κB, and HIF-1α. These results suggest that DMBT can inhibit CNV by down-regulation of VEGF in retina through Akt/NF-κB/HIF-1α and ERK/Nrf2/HO-1/HIF-1α pathway. DMBT might be a promising lead molecule for anti-CNV and serve as a therapeutic agent to inhibit CNV.


Assuntos
Neovascularização de Coroide/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Trealose/análogos & derivados , Fator A de Crescimento do Endotélio Vascular/metabolismo , Linhagem Celular , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Degeneração Macular/tratamento farmacológico , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Trealose/farmacologia
8.
J Biol Chem ; 289(19): 12989-99, 2014 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-24692543

RESUMO

Excessive absorption of intestinal cholesterol is a risk factor for atherosclerosis. This report examines the effect of cholecystokinin (CCK) on plasma cholesterol level and intestinal cholesterol absorption using the in vivo models of C57BL/6 wild-type and low density lipoprotein receptor knock-out (LDLR(-/-)) mice. These data were supported by in vitro studies involving mouse primary intestinal epithelial cells and human Caco-2 cells; both express CCK receptor 1 and 2 (CCK1R and CCK2R). We found that intravenous injection of [Thr(28),Nle(31)]CCK increased plasma cholesterol levels and intestinal cholesterol absorption in both wild-type and LDLR(-/-) mice. Treatment of mouse primary intestinal epithelial cells with [Thr(28),Nle(31)]CCK increased cholesterol absorption, whereas selective inhibition of CCK1R and CCK2R with antagonists attenuated CCK-induced cholesterol absorption. In Caco-2 cells, CCK enhanced CCK1R/CCK2R heterodimerization. Knockdown of both CCK1R and CCK2 or either one of them diminished CCK-induced cholesterol absorption to the same extent. CCK also increased cell surface-associated NPC1L1 (Niemann-Pick C1-like 1) transporters but did not alter their total protein expression. Inhibition or knockdown of NPC1L1 attenuated CCK-induced cholesterol absorption. CCK enhanced phosphatidylinositide 3-kinase (PI3K) and Akt phosphorylation and augmented the interaction between NPC1L1 and Rab11a (Rab-GTPase-11a), whereas knockdown of CCK receptors or inhibition of G protein ßγ dimer (Gßγ) diminished CCK-induced PI3K and Akt phosphorylation. Inhibition of PI3K and Akt or knockdown of PI3K diminished CCK-induced NPC1L1-Rab11a interaction and cholesterol absorption. Knockdown of Rab11a suppressed CCK-induced NPC1L1 translocation and cholesterol absorption. These data imply that CCK enhances cholesterol absorption by activation of a pathway involving CCK1R/CCK2R, Gßγ, PI3K, Akt, Rab11a, and NPC1L.


Assuntos
Colecistocinina/metabolismo , Colesterol/metabolismo , Hipercolesterolemia/metabolismo , Absorção Intestinal , Mucosa Intestinal/metabolismo , Regulação para Cima , Animais , Células CACO-2 , Colecistocinina/genética , Colesterol/genética , Humanos , Hipercolesterolemia/genética , Hipercolesterolemia/patologia , Intestinos/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Camundongos Knockout , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/genética , Transporte Proteico/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor de Colecistocinina B/genética , Receptor de Colecistocinina B/metabolismo , Transdução de Sinais/genética , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo
9.
J Biol Chem ; 288(21): 14815-23, 2013 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-23592778

RESUMO

Solute carrier family 7, member 11 (Slc7a11) is a plasma membrane cystine/glutamate exchanger that provides intracellular cystine to produce glutathione, a major cellular antioxidant. Oxidative and endoplasmic reticulum stresses up-regulate Slc7a11 expression by activation of nuclear factor erythroid 2-related factor 2 and transcription factor 4. This study examined the effect of ethanol on Slc7a11 expression and the underlying mechanism involved. Treatment of mouse hepatic stellate cells with ethanol significantly increased Slc7a11 mRNA and protein levels. Deletion of a 20-bp DNA sequence between -2044 to -2024 upstream of the transcription start site significantly increased basal activity and completely abolished the ethanol-induced activity of the Slc7a11 promoter. This deletion did not affect Slc7a11 promoter activity induced by oxidative or endoplasmic reticulum stress. DNA sequence analysis revealed a binding motif for octamer-binding transcription factor 1 (OCT-1) in the deleted fragment. Mutation of this OCT-1 binding motif resulted in a similar effect as the deletion experiment, i.e. it increased the basal promoter activity and abolished the response to ethanol. Ethanol exposure significantly inhibited OCT-1 binding to the Slc7a11 promoter region, although it did not alter OCT-1 mRNA and protein levels. OCT-1 reportedly functions as either a transcriptional enhancer or repressor, depending on the target genes. Results from this study suggest that OCT-1 functions as a repressor on the Slc7a11 promoter and that ethanol inhibits OCT-1 binding to the Slc7a11 promoter, thereby increasing Slc7a11 expression. Taken together, inhibition of the DNA binding activity of transcriptional repressor OCT-1 is a mechanism by which ethanol up-regulates Slc711 expression.


Assuntos
Sistema y+ de Transporte de Aminoácidos/biossíntese , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Fator 1 de Transcrição de Octâmero/metabolismo , Proteínas Repressoras/metabolismo , Elementos de Resposta , Regulação para Cima/efeitos dos fármacos , Motivos de Aminoácidos , Sistema y+ de Transporte de Aminoácidos/genética , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/metabolismo , Camundongos , Camundongos Transgênicos , Fator 1 de Transcrição de Octâmero/genética , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Proteínas Repressoras/genética , Deleção de Sequência , Regulação para Cima/genética
10.
Med Sci Monit ; 20: 2082-7, 2014 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-25351338

RESUMO

BACKGROUND: It is currently unclear whether the degree of stenosis or the cerebrovascular reserve (CVR) is a better predictor of ischemic stroke. MATERIAL AND METHODS: In this study, CVR was measured by perfusion computed tomography with inhalation of 5% CO2 in 37 symptomatic patients with internal carotid artery (ICA) or middle cerebral artery (MCA) stenosis or occlusion. Patients were divided into groups according to the degree of stenosis: ≥70% stenosis (stenosis group 1) or <70% stenosis (stenosis group 2); and according to CVR: ≥10% CVR (CVR group 1) or <10% CVR (CVR group 2). All patients were given medical treatment. RESULTS: During a mean follow-up period of 56.9 months (range 24-73 months), recurrent ipsilateral ischemic stroke occurred in 7 patients. Ischemic stroke occurred in 0 of 19 patients in CVR group 1 (annual risk 0%), 7 of 18 patients in CVR group 2 (annual risk 7.7%), 3 of 18 patients in stenosis group 1 (annual risk 3.3%), and 4 of 19 patients in stenosis group 2 (annual risk 4.7%). Comparisons using Pearson's chi-square test showed a significant difference in the rate of ischemic stroke between CVR group 1 and CVR group 2 (odds ratio 1.700; 95% confidence interval 1.142-2.530; P=0.003), but no significant difference between stenosis group 1 and stenosis group 2 (P=0.691). CONCLUSIONS: Cerebrovascular reserve may be a more accurate predictor of stroke than degree of ICA or MCA stenosis.


Assuntos
Encéfalo/fisiopatologia , Constrição Patológica/fisiopatologia , Artéria Cerebral Média/patologia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva
11.
Brain Sci ; 14(8)2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39199480

RESUMO

BACKGROUND: Cognitive impairment is common in patients with Parkinson's disease (PD) and occurs through multiple mechanisms, including Alzheimer's disease (AD) pathology and the involvement of α-synucleinopathies. We aimed to investigate the pathological biomarkers of both PD and AD in plasma and neuronal extracellular vesicles (EVs) and their association with different types of cognitive impairment in PD patients. METHODS: A total of 122 patients with PD and 30 healthy controls were included in this cross-sectional cohort study between March 2021 and July 2023. Non-dementia PD patients were divided into amnestic and non-amnestic groups according to the memory domain of a neuropsychological assessment. Plasma and neuronal EV biomarkers, including α-synuclein (α-syn), beta-amyloid (Aß), total tau (T-tau), phosphorylated tau181 (p-tau181), and glial fibrillary acidic protein (GFAP), were measured using a single-molecule array and a chemiluminescence immunoassay, respectively. RESULTS: Neuronal EV but not plasma α-syn levels, were significantly increased in PD as compared to healthy controls, and they were positively associated with UPDRS part III scores and the severity of cognitive impairment. A lower plasma Aß42 level and higher neuronal EV T-tau level were found in the amnestic PD group compared to the non-amnestic PD group. CONCLUSIONS: The results of the current study demonstrate that neuronal EV α-syn levels can be a sensitive biomarker for assisting in the diagnosis and disease severity prediction of PD. Both AD and PD pathologies are important factors in cognitive impairment associated with PD, and AD pathologies are more involved in amnestic memory deficit in PD.

12.
J Biol Chem ; 287(6): 3751-9, 2012 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-22170052

RESUMO

Activation of very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (apoER2) results in either pro- or anti-atherogenic effects depending on the ligand. Using reelin and apoE as ligands, we studied the impact of VLDLR- and apoER2-mediated signaling on the expression of ATP binding cassette transporter A1 (ABCA1) and cholesterol efflux using RAW264.7 cells. Treatment of these mouse macrophages with reelin or human apoE3 significantly increased ABCA1 mRNA and protein levels, and apoAI-mediated cholesterol efflux. In addition, both reelin and apoE3 significantly increased phosphorylated disabled-1 (Dab1), phosphatidylinositol 3-kinase (PI3K), protein kinase Cζ (PKCζ), and specificity protein 1 (Sp1). This reelin- or apoER2-mediated up-regulation of ABCA1 expression was suppressed by 1) knockdown of Dab1, VLDLR, and apoER2 with small interfering RNAs (siRNAs), 2) inhibition of PI3K and PKC with kinase inhibitors, 3) overexpression of kinase-dead PKCζ, and 4) inhibition of Sp1 DNA binding with mithramycin A. Activation of the Dab1-PI3K signaling pathway has been implicated in VLDLR- and apoER2-mediated cellular functions, whereas the PI3K-PKCζ-Sp1 signaling cascade has been implicated in the regulation of ABCA1 expression induced by apoE/apoB-carrying lipoproteins. Taken together, these data support a model in which activation of VLDLR and apoER2 by reelin and apoE induces ABCA1 expression and cholesterol efflux via a Dab1-PI3K-PKCζ-Sp1 signaling cascade.


Assuntos
Transportadores de Cassetes de Ligação de ATP/biossíntese , Moléculas de Adesão Celular Neuronais/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Proteínas Relacionadas a Receptor de LDL/metabolismo , Macrófagos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores de LDL/metabolismo , Serina Endopeptidases/metabolismo , Transdução de Sinais/fisiologia , Regulação para Cima/fisiologia , Transportador 1 de Cassete de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Apolipoproteína E3/genética , Apolipoproteína E3/metabolismo , Moléculas de Adesão Celular Neuronais/genética , Linhagem Celular , Colesterol/genética , Colesterol/metabolismo , Proteínas da Matriz Extracelular/genética , Técnicas de Silenciamento de Genes , Humanos , Proteínas Relacionadas a Receptor de LDL/genética , Camundongos , Proteínas do Tecido Nervoso/genética , Proteína Quinase C-épsilon/genética , Proteína Quinase C-épsilon/metabolismo , Receptores de LDL/genética , Proteína Reelina , Serina Endopeptidases/genética , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismo
13.
J Hand Surg Am ; 38(11): 2169-72, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24021738

RESUMO

We present the case of a 22-year-old man with third- to fourth-degree flame burns to all fingers of the right hand. After removing the necrotic tissues and amputating the carbonized distal segments of each finger, we covered the injured thumb with a paraumbilical tubular flap and covered the other fingers with an abdominal wall marsupial flap. Fifty days after injury, all the wounds healed, and the remaining fingers were salvaged. Four months after injury, the grip strength and the first web span of the right hand was 23.6 kg and 53°, and the patient could fulfill almost all the activities of daily living.


Assuntos
Queimaduras/cirurgia , Traumatismos dos Dedos/cirurgia , Amputação Cirúrgica , Queimaduras/patologia , Traumatismos dos Dedos/patologia , Força da Mão , Humanos , Masculino , Necrose , Recuperação de Função Fisiológica , Retalhos Cirúrgicos , Polegar/lesões , Adulto Jovem
14.
Front Plant Sci ; 14: 1303398, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38317838

RESUMO

Messenger RNA polyadenylation, the process wherein the primary RNA polymerase II transcript is cleaved and a poly(A) tract added, is a key step in the expression of genes in plants. Moreover, it is a point at which gene expression may be regulated by determining the functionality of the mature mRNA. Polyadenylation is mediated by a complex (the polyadenylation complex, or PAC) that consists of between 15 and 20 subunits. While the general functioning of these subunits may be inferred by extending paradigms established in well-developed eukaryotic models, much remains to be learned about the roles of individual subunits in the regulation of polyadenylation in plants. To gain further insight into this, we conducted a survey of variability in the plant PAC. For this, we drew upon a database of naturally-occurring variation in numerous geographic isolates of Arabidopsis thaliana. For a subset of genes encoding PAC subunits, the patterns of variability included the occurrence of premature stop codons in some Arabidopsis accessions. These and other observations lead us to conclude that some genes purported to encode PAC subunits in Arabidopsis are actually pseudogenes, and that others may encode proteins with dispensable functions in the plant. Many subunits of the PAC showed patterns of variability that were consistent with their roles as essential proteins in the cell. Several other PAC subunits exhibit patterns of variability consistent with selection for new or altered function. We propose that these latter subunits participate in regulatory interactions important for differential usage of poly(A) sites.

15.
Front Neurol ; 14: 1149577, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37533464

RESUMO

Introduction: Orthostatic hypotension (OH) frequently accompanies autonomic dysfunction and is an important risk factor for cognitive impairment in Parkinson's disease (PD). However, the association between different cognitive functions and OH in PD patients is not yet fully understood. Methods: This study aimed to evaluate the scores of different cognitive domains and multiple parameters using different imaging techniques on PD patients with or without OH. A total number of 31 PD patients with OH (n = 20) and without OH (n = 11) were recruited from the Department of Neurology, Beijing Xuanwu Hospital for this study. All patients underwent beat-to-beat non-invasive blood pressure recordings and an active standing test to evaluate neurogenic OH and a global neuropsychological test to assess cognitive function. All patients underwent dynamic cerebral autoregulation (dCA) measurement, brain magnetic resonance imaging (MRI), and brain 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Results: The results showed that OH patients had poor delayed recall verbal memory when compared with the PD patients without OH (1.75 ± 1.59 vs. 3.10 ± 1.73, p = 0.042). The dCA test indicated a significant difference in the right very low-frequency (VLF) gain between two groups (1.27 ± 0.17 vs. 1.10 ± 0.26, p = 0.045) and the brain 18F-FDG PET/CT indicated a significant difference in the SUV (right medial temporal lobe) to SUV (occipital lobe) ratio (0.60 ± 0.08 vs. 0.67 ± 0.11, p = 0.049). Meanwhile, these two imaging parameters were negatively correlated (p < 0.001). Furthermore, the score of a delayed recall verbal memory in the OH group was positively correlated with the right medial temporal lobe to occipital lobe ratio (p < 0.001) and was negatively correlated with the right VLF gain (p = 0.023). Discussion: PD with OH patients had poor delayed recall memory, which might have been caused by the decreased metabolic dysfunction of specific medial temporal lobe due to the impaired dCA ability.

16.
ACS Macro Lett ; 12(5): 653-658, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37155319

RESUMO

Thermally insulating aerogels can now be prepared from ceramics, polymers, carbon, and metals and composites between them. However, it is still a great challenge to make aerogels with high strength and excellent deformability. We propose a design concept of hard cores and flexible chains that alternately construct the aerogel skeleton structure. The approach gives the designed SiO2 aerogel excellent compressive (fracture strain 83.32%), tensile. and shear deformabilities, corresponding to maximum strengths of 22.15, 1.18, and 1.45 MPa, respectively. Also, the SiO2 aerogel can stably perform 100 load-unload cycles at a 70% large compression strain, demonstrating an excellent resilient compressibility. In addition, the low density of 0.226 g/cm3, the high porosity of 88.7%, and the average pore size of 45.36 nm effectively inhibit heat conduction and heat convection, giving the SiO2 aerogel outstanding thermal insulation properties [0.02845 W/(m·K) at 25 °C and 0.04895 W/(m·K) at 300 °C], and the large number of hydrophobic groups itself also gives it excellent hydrophobicity and hydrophobic stability (hydrophobic angle of 158.4° and saturated mass moisture absorption rate of about 0.327%). The successful practice of this concept has provided different insights into the preparation of high-strength aerogels with high deformability.

17.
J Biol Chem ; 286(11): 8917-23, 2011 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-21257755

RESUMO

ATP-binding cassette transporter A1 (ABCA1) is a membrane-bound protein that regulates the efflux of cholesterol derived from internalized lipoproteins. Using a mouse macrophage cell line, this report studied the impact of low-density lipoproteins (LDL) on ABCA1 expression and the signaling pathway responsible for lipoprotein-induced ABCA1 expression. Our data demonstrated that treatment of macrophages with LDL increased ABCA1 mRNA and protein levels 4.3- and 3.5-fold, respectively. LDL also induced an ∼2-fold increase in macrophage surface expression of ABCA1 and a 14-fold-increase in apolipoprotein AI-mediated cholesterol efflux. In addition, LDL significantly increased the level of phosphorylated specificity protein 1 (Sp1) and the amount of Sp1 bound to the ABCA1 promoter without alteration in total Sp1 protein level. Mutation of the Sp1 binding site in the ABCA1 promoter and inhibition of Sp1 DNA binding with mithramycin A suppressed the ABCA1 promoter activity and reduced the ABCA1 expression level induced by LDL. LDL treatment also elevated protein kinase C-ζ (PKC-ζ) phosphorylation and induced PKC-ζ binding with Sp1. Inhibition of PKC-ζ with kinase inhibitors or overexpression of kinase-dead PKC-ζ attenuated Sp1 phosphorylation and ABCA1 expression induced by LDL. These results demonstrate for the first time that activation of the PKCζ-Sp1 signaling cascade is a mechanism for regulation of LDL-induced ABCA1 expression.


Assuntos
Transportadores de Cassetes de Ligação de ATP/biossíntese , Regulação da Expressão Gênica/fisiologia , Elementos de Resposta/fisiologia , Transdução de Sinais/fisiologia , Transcrição Gênica/fisiologia , Transportador 1 de Cassete de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Linhagem Celular , Colesterol/genética , Colesterol/metabolismo , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacologia , Camundongos , Camundongos Knockout , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Plicamicina/análogos & derivados , Plicamicina/farmacologia , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismo , Transcrição Gênica/efeitos dos fármacos
18.
Sheng Li Ke Xue Jin Zhan ; 43(6): 411-6, 2012 Dec.
Artigo em Zh | MEDLINE | ID: mdl-23520758

RESUMO

Repetitive transcranial of magnetic stimulation (rTMS), as a new electrophysiological technique, has been used in treating neurological and psychiatric diseases in clinical. In recent years, rTMS has also been employed to explore the treatment options for post stroke cognitive impairment (PSCI). Studies showed that rTMS was beneficial to recovery of post-stroke aphasia, improvement of memory dysfunction and alleviation of hemispatial neglect. Moreover, it is safe for patient within the recommended parameters of safety guidance. rTMS exerts therapeutic effects by interfering with the reconstruction of cortical network, improving the cerebral blood flow and metabolism, adjusting the ion balance by modulating cortical excitability. In addition, rTMS could enhance synaptic plasticity, inhibit the apoptosis, and regulate the transmission of a variety of neurotransmitters. It was reviewed that the basic principles of rTMS, the efficacy, safety and mechanism of rTMS in the treatment of PSCI, as well as the current problems and prospects in this paper.


Assuntos
Córtex Cerebral/fisiopatologia , Transtornos Cognitivos/terapia , Acidente Vascular Cerebral/terapia , Estimulação Magnética Transcraniana/métodos , Animais , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Humanos , Plasticidade Neuronal/efeitos da radiação , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia
19.
Front Psychol ; 13: 915443, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35645872

RESUMO

This paper takes laptops as an example to carry out research on quantitative model of brand recognition based on sentiment analysis of big data. The basic idea is to use web crawler technology to obtain the most authentic and direct information of different laptop brands from first-line consumers from public spaces such as buyer reviews of major e-commerce platforms, including review time, text reviews, satisfaction ratings and relevant user information, etc., and then analyzes consumers' sentimental tendencies and recognition status of the product brands. This study extracted a total of 437,815 user reviews of laptops from e-commerce platforms from January 1, 2019 to December 31, 2021, and performed data preprocessing on the obtained review data, followed by sentiment dictionary construction, attribute expansion, text quantification and algorithm evaluation. This paper analyzed the information receiving and processing hierarchy of the quantitative model of brand recognition, discussed the interactive relationship between brand recognition and consumer sentiment, discussed the brand recognition bias, style and demand in the context of big data, and performed the sentiment statistics and dimension analysis in the quantitative model of brand recognition. The study results show that the quantitative model of brand recognition based on sentiment analysis of big data can transform and map the keywords in text to word vectors in the high-dimensional semantic space by performing unsupervised machine learning on the text based on artificial neural network computer bionic metaphors; the model can accumulate each brand-related buyer review in the corresponding brand recognition dimension, so as to obtain the value of each product in each dimension of brand recognition; finally, the model will add the values of each dimension of brand recognition, that is, obtain the relevant value of the sum of each brand recognition. The results of this paper may provide a reference for further research on the quantitative model of brand recognition based on sentiment analysis of big data.

20.
Neurosciences (Riyadh) ; 16(4): 335-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21983376

RESUMO

OBJECTIVE: To explore whether antiplatelet (AP) agent therapy increased intracranial hemorrhage (ICH) incidence and reduced ischemic stroke recurrence. METHODS: A single-center retrospective cohort study involving 256 cases from 336 Chinese in-patients who had ischemic stroke with ICH history in Beijing Chaoyang Hospital, Beijing, China between May 2005 and October 2009 was conducted. Subjects were divided into 2 groups (with AP and without AP), followed by stroke events for 12-38 months. Logistic regression analysis was used to evaluate the effects of AP on cerebral infarction and ICH recurrence. RESULTS: The AP agent did not increase ICH recurrence in the secondary prevention of ischemic stroke with ICH history (odds ratio [OR] 1.431, confidence interval [CI] 0.198-2.467, p=0.577). Hypertension and lobar hemorrhage were risk factors of ICH recurrence. However, there was no statistical difference between recurrence of lobar hemorrhage and AP use (x2=0.516, p=0.468). The AP agent significantly decreased the incidence of cerebral infarction (OR 0.424, CI 0.190-0.950, p=0.037). CONCLUSION: The AP agents may be beneficial to secondary prevention of ischemic stroke with ICH history, with no increased incidence of cerebral hemorrhage. It would be safer to maintain blood pressure in the normal range and to exclude lobar hemorrhage when AP is used.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/prevenção & controle , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/etnologia , Inibidores da Agregação Plaquetária/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Isquemia Encefálica/etnologia , China/epidemiologia , Estudos de Coortes , Feminino , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Retrospectivos , Prevenção Secundária
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