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BACKGROUND: Schizophrenia is a widespread and debilitating mental disorder. However, the underlying molecular mechanism of schizophrenia remains largely unknown and no objective laboratory tests are available to diagnose this disorder. The aim of the present study was to characterize the alternations of glucose metabolites and identify potential diagnostic biomarkers for schizophrenia. METHODS: Gas chromatography/mass spectrometry based targeted metabolomic method was used to quantify the levels of 13 glucose metabolites in peripheral blood mononuclear cells (PBMCs) derived from healthy controls, schizophrenia and major depression subjects (n = 55 for each group). RESULTS: The majority (84.6%) of glucose metabolites were significantly disturbed in schizophrenia subjects, while only two (15.4%) glucose metabolites were differently expressed in depression subjects relative to healthy controls in both training set (n = 35/group) and test set (n = 20/group). Antipsychotics had only a subtle effect on glucose metabolism pathway. Moreover, ribose 5-phosphate in PBMCs showed a high diagnostic performance for first-episode drug-naïve schizophrenia subjects. CONCLUSION: These findings suggested disturbance of glucose metabolism may be implicated in onset of schizophrenia and could aid in development of diagnostic tool for this disorder.
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Glucose/metabolismo , Leucócitos Mononucleares/metabolismo , Metabolômica/métodos , Esquizofrenia/metabolismo , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Demografia , Transtorno Depressivo Maior/metabolismo , Feminino , Humanos , Masculino , MetabolomaRESUMO
The role of A1 adenosine receptors (A1ARs) in the white matter under chronic cerebral ischemic conditions remains unclear. Here, we used right unilateral common carotid artery occlusion (rUCCAO) to construct a chronic cerebral ischemic mouse model. A1AR expression and proteolipid protein (PLP, a marker of white matter myelination) in the corpus callosum were observed by immunoreaction and immunohistochemistry, respectively. Pro-inflammatory interleukin-1ß (IL-1ß) and anti-inflammatory interleukin-10 (IL-10) levels were determined by ELISA. The Morris water maze test was employed to detect cognitive impairment. A1AR expression significantly decreased in the rUCCAO group as compared with the sham control group on weeks 2, 4, and 6, respectively. IL-10 levels in the rUCCAO group significantly declined on week 6, while there was no significant change in IL-1ß expression. PLP expression significantly decreased in the rUCCAO group on weeks 2, 4, and 6. Moreover, latency time for the Morris water maze test significantly increased in the rUCCAO group on weeks 4 and 6, while the number of platform location crossing significantly decreased in the rUCCAO group on weeks 2, 4, and 6. In conclusion, this study provides the first evidence that chronic cerebral ischemia appears to induce A1AR downregulation and inhibition of IL-10 production, which may play key roles in the neuropathological mechanisms of ischemic white matter lesions. These data will facilitate future studies in formulating effective therapeutic strategies for ischemic white matter lesions.
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Isquemia Encefálica/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/fisiologia , Receptor A1 de Adenosina/metabolismo , Substância Branca/metabolismo , Fatores Etários , Animais , Isquemia Encefálica/patologia , Doença Crônica , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Substância Branca/patologiaRESUMO
As a complex mental process, creativity requires the coordination of multiple brain regions. Previous pathological research on figural creativity has indicated that there is a mechanism by which the left side of the brain inhibits the activities of the right side of the brain during figural creative thinking, but this mechanism has not been directly demonstrated. In this study, we used functional magnetic resonance imaging (fMRI) to demonstrate the existence of this inhibitory mechanism in young adults (15 women, 11 men, mean age: 22 years) that were not artists. By making comparisons between brain activity during creative and uncreative tasks, we found increased activity in the left middle and inferior frontal lobe and strong decreases in activity in the right middle frontal lobe and the left inferior parietal lobe. As such, these data suggest that the left frontal lobe may inhibit the right hemisphere during figural creative thinking in normal people. Moreover, removal of this inhibition by practicing artistry or through specific damage to the left frontal lobe may facilitate the emergence of artistic creativity.
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Arte , Mapeamento Encefálico , Córtex Cerebral/fisiologia , Criatividade , Dominância Cerebral/fisiologia , Imaginação/fisiologia , Inibição Psicológica , Imageamento por Ressonância Magnética , Pensamento/fisiologia , Adulto , Feminino , Lobo Frontal/fisiologia , Humanos , Masculino , Modelos Neurológicos , Modelos Psicológicos , Lobo Parietal/fisiologia , Estimulação Luminosa , Córtex Pré-Frontal/fisiologia , Adulto JovemRESUMO
The antioxidant activity of corn peptides is related to their molecular weight and structure. Corn gluten meal (CGM) was hydrolyzed using a combination of Alcalase, Flavorzyme and Protamex, and the hydrolysates were subjected to antioxidant activity analysis after further fractionation. Corn peptides with molecular weights less than 1 kDa (CPP1) exhibited excellent antioxidant activity. A novel peptide, Arg-Tyr-Leu-Leu (RYLL), was identified from CPP1. RYLL displayed preferable scavenging capacities for ABTS radicals and DPPH radicals, with IC50 values of 0.122 mg/ml and 0.180 mg/ml, respectively. Based on quantum calculations, RYLL had multiple antioxidant active sites, and tyrosine was the main active site due to the highest energy of the highest occupied molecular orbit (HOMO). Moreover, the simple peptide structure and hydrogen bond network of RYLL contributed to the exposure of the active site. This study elucidated the antioxidant mechanism of corn peptides, which could provide an understanding for CGM hydrolysates as natural antioxidants.
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Antioxidantes , Glutens , Antioxidantes/química , Glutens/química , Zea mays/química , Hidrólise , Peptídeos/química , Hidrolisados de Proteína/químicaRESUMO
This study aimed to evaluate the effects of different dietary pantothenic acid levels on growth performance, carcass traits, and plasma biochemical parameters of starter Pekin ducks from 1 to 21 days of age, as well as the pantothenic acid requirement of starter ducks. A total of 384 one-day-old male white Pekin ducklings were assigned randomly into 6 dietary treatments, each with 8 replicate pens of 8 ducks. Ducks were fed conventional basal corn-soybean diets containing 8.5, 10.5, 12.5, 14.5, 16.5, and 18.5 mg/kg pantothenic acid for 21 days. Growth depression, poor pantothenic acid status, fasting hypoglycemia, and elevated plasma uric acid (UA) content were observed in the ducks fed the pantothenic acid-deficient basal diet (p < 0.05), and these adverse effects were ameliorated by pantothenic acid supplementation. Among all ducks, the birds fed the basal diet with no supplementation of pantothenic acid had the lowest body weight, average daily weight gain (ADG), average daily feed intake (ADFI), breast meat yield, and plasma pantothenic acid and glucose contents (p < 0.05), and the greatest plasma UA content (p < 0.05). In addition, all these parameters showed a linear or quadratic response as dietary pantothenic acid levels increased (p < 0.05). According to broken-line regression, the pantothenic acid requirements of starter male white Pekin ducks for body weight, ADG, and plasma pantothenic acid content were 13.36, 13.29, and 15.0 mg/kg, respectively. The data potentially provides theoretical support for the utilization of pantothenic acid in duck production.
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The experiment was conducted to evaluate the effects of five rubber seed oil (RSO) levels (0, 1%, 2%, 4%, and 6%) on hens laying performance, egg quality, and yolks fatty acid composition and cholesterol contents. Three hundred and sixty 30-week-old Lohmann Brown laying hens were allotted to 5 groups. The results showed that the egg production was increased in 4% RSO group (Pâ¯<â¯0.05), but egg quality parameters and the contents of dry matter, lipid, and protein in yolks were not influenced among treatments (Pâ¯>â¯0.05). Yolk cholesterol contents were reduced in RSO supplemental groups (Pâ¯<â¯0.05). The concentration of total n-3 PUFA in yolks increased gradually while the ratio of n-6/n-3 decreased gradually with increasing dietary RSO levels (Pâ¯<â¯0.001). In conclusion, dietary RSO supplementation increased yolk n-3 PUFA levels, improved yolk color, and reduced yolk cholesterol contents without negative influence on laying performance parameters.
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Ração Animal , Galinhas , Colesterol/metabolismo , Gema de Ovo/química , Gorduras Insaturadas/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Animais , Galinhas/metabolismo , Colesterol/análise , Suplementos Nutricionais , Gema de Ovo/metabolismo , Ácidos Graxos Ômega-3/análise , Feminino , Qualidade dos Alimentos , Armazenamento de Alimentos , Lipídeos/análiseRESUMO
To explore the brainstem injury associated with supratentorial lesions, we conducted analysis of ICP levels and detected ENG parameters by using the cold caloric reflex test and histopathological examinations of the brainstem. Rat model of intracerebral hemorrhage was well-established in the study of supratentorial lesions of varying severities (n=210). Intracerebral pressure monitoring and electronystagmography of the cold caloric reflex test were simultaneously performed in animals. Apoptotic, immunohistochemical, and histopathological changes in different segments of the brainstem were investigated at various time intervals. Electronystagmography parameters were analyzed by cold caloric reflex test. The result showed that the increase of intracerebral pressure was correlated with lesion severity including elevating levels and rostral-caudal progression of neuronal apoptosis, demyelination, N-methyl-D-aspartate cell receptor down-regulation (r=0.815), and histopathological changes. Mutiple discrimination analysis of electronystagmography parameters presented a diagnostic accuracy rate of 79.5% in localizing brainstem injury. In conclusion, our data demonstrated that electronystagmography monitoring along with the cold caloric reflex test performed a favorable effect on the estimation of brainstem injury in ICH rat model, which provided a potential bedside diagnostic tool to assess and predict the progress of supratentorial lesion patient in future.
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We performed a meta-analysis to clarify the relationship between long chain n-3 polyunsaturated fatty acid (PUFA) intake and stroke risk. Relevant studies were identified by searching online databases through May 2015. Log relative risks (RRs) of the highest versus the lowest for cohort studies were weighed by the inverse variance method to obtain pooled RRs. Fourteen prospective cohort studies including 514,483 individuals and 9,065 strokes were included. The pooled RR of overall stroke risk for long chain n-3 PUFA intake was 0.87 [95% confidence interval (CI), 0.79-0.95]. Stratification analysis showed that higher long chain n-3 PUFAs intake was associated with reduced fatal stroke risk (RR = 0.84; 95% CI, 0.73-0.97), reduced stroke risk for BMI < 24 (RR = 0.86; 95% CI, 0.75-0.98) and reduced stroke risk for females (RR = 0.81; 95% CI, 0.71-0.92), but was not associated with stroke risk for either BMI ≥ 24 or men. This meta-analysis reveals that higher long chain n-3 PUFA intake is inversely associated with risk of stroke morbidity and mortality with BMI and sex as key factors influencing this risk. Individuals should be encouraged to manage their body weight while increasing their intake of long chain n-3 PUFAs.
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Índice de Massa Corporal , Dieta , Ácidos Graxos Ômega-3 , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Feminino , Humanos , Masculino , Razão de Chances , Estudos Prospectivos , Viés de Publicação , RiscoRESUMO
Bipolar disorder (BD) is a debilitating mental disorder that cannot be diagnosed by objective laboratory-based modalities. Our previous studies have independently used nuclear magnetic resonance (NMR)-based and gas chromatography-mass spectrometry (GC-MS)-based metabonomic methods to characterize the urinary metabolic profiles of BD subjects and healthy controls (HC). However, the combined application of NMR spectroscopy and GC-MS may identify a more comprehensive metabolite panel than any single metabonomic platform alone. Therefore, here we applied a dual platform (NMR spectroscopy and GC-MS) that generated a panel of five metabolite biomarkers for BD-four GC-MS-derived metabolites and one NMR-derived metabolite. This composite biomarker panel could effectively discriminate BD subjects from HC, achieving an area under receiver operating characteristic curve (AUC) values of 0.974 in a training set and 0.964 in a test set. Moreover, the diagnostic performance of this panel was significantly superior to the previous single platform-derived metabolite panels. Thus, the urinary biomarker panel identified here shows promise as an effective diagnostic tool for BD. These findings also demonstrate the complementary nature of NMR spectroscopy and GC-MS for metabonomic analysis, suggesting that the combination of NMR spectroscopy and GC-MS can identify a more comprehensive metabolite panel than applying each platform in isolation.
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Transtorno Bipolar/diagnóstico , Transtorno Bipolar/urina , Metaboloma , Metabolômica/estatística & dados numéricos , Adulto , Área Sob a Curva , Biomarcadores/urina , Transtorno Bipolar/fisiopatologia , Estudos de Casos e Controles , Análise Discriminante , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Imageamento por Ressonância Magnética , Masculino , Metabolômica/métodos , Curva ROCRESUMO
Fluoxetine is a widely used antidepressant drug which inhibits the reuptake of serotonin in the central nervous system (CNS). Recent studies have shown that fluoxetine can promote neurogenesis and improve the survival rate of neurons. However, whether fluoxetine modulates the neuroprotection of neural stem cells (NSCs) needs to be elucidated. In this study, we demonstrated that 50 µM fluoxetine significantly upregulated expression of the phosphorylated-AKT and ERK1/2 proteins in NSCs derived from rats. Besides, expression of phosphorylated-AKT and phosphorylated-ERK1/2 in fluoxetine-treated NSCs was effectively blocked (P<0.05) by both PI3-K inhibitor (LY294002) and MEK inhibitor (PD98059). It was, therefore, concluded that the crosstalk between PI3K/AKT and MAPK/ERK pathways involved AKT and ERK1/2 phosphorylation by fluoxetine treatment. This study points to a novel role of fluoxetine in neuroprotection as an antidepressant drug and also unravels the crosstalk mechanism between the two signaling pathways.
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MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fluoxetina/farmacologia , Sistema de Sinalização das MAP Quinases , Células-Tronco Neurais/enzimologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Regulação para Cima/efeitos dos fármacos , Animais , Expressão Gênica/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos WistarRESUMO
The present work explored the anti-neuroinflammation effects of Ginseng Rb1 in a rat model of Alzheimer disease produced by ventricle injection of Aß1-42. Aß1-42 injection induces loss of learning and memory behavior of rats in Morris water maze, which could be reversed with Rb1 treatment. Further, Rb1 reversed the changes in several direct or indirect neuroinflammation markers in the hippocampus, suggesting that this could be a potential underlying mechanism and a way to develop anti-aging drugs.