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1.
Mol Med Rep ; 21(6): 2633-2641, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32323790

RESUMO

The PTEN induced putative kinase 1 (PINK1) mutation is the second most common cause of autosomal recessive adolescent Parkinson's disease (PD). Furthermore, mitochondrial disorders and oxidative stress are important mechanisms in the pathogenesis of PD. Numerous members of the Wnt family have been found to be associated with neurodegenerative diseases. Therefore, the present study investigated the role of the Wnt2 gene in PINK1B9 transgenic flies, which is a PD model, and its underlying mechanism. It was identified that overexpression of Wnt2 reduced the abnormality rate of PD transgenic Drosophila and improved their flight ability, while other intervention groups had no significant effect. Furthermore, an increase in ATP concentration normalized mitochondrial morphology, and increased the mRNA expression levels of NADH­ubiquinone oxidoreductase chain 1 (ND1), ND42, ND75, succinate dehydrogenase complex subunits B, Cytochrome b and Cyclooxygenase 1, which are associated with Wnt2 overexpression. Moreover, overexpression of Wnt2 in PD transgenic Drosophila resulted in the downregulation of reactive oxygen species and malondialdehyde production, and increased manganese superoxide dismutase (MnSOD), while glutathione was not significantly affected. It was found that overexpression of Wnt2 did not alter the protein expression of ß­catenin in PINK1B9 transgenic Drosophila, but did increase the expression levels of PPARG coactivator 1α (PGC­1α) and forkhead box sub­group O (FOXO). Collectively, the present results indicated that the Wnt2 gene may have a protective effect on PD PINK1B9 transgenic Drosophila. Thus, it was speculated that the reduction of oxidative stress and the restoration of mitochondrial function via Wnt2 overexpression may be related to the PGC­1α/FOXO/MnSOD signaling pathway in PINK1 mutant transgenic Drosophila.

2.
PeerJ ; 7: e7357, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531265

RESUMO

Background: Adolescence is a vulnerable period of life, and many mental health and behavioral problems emerge during this particular period, including depression, internet addiction (IA), and suicidal behaviors. Poor quality of life (QOL) and IA have been found to be significantly associated with suicidal ideation (SI) among Chinese university students, of whom most have been adults. Nevertheless, their associations with SI are rarely studied among Chinese adolescents. The objective of this study was to examine these relationships in a representative adolescent sample of Chinese senior high school students, who are experiencing an enormous transition from childhood to adulthood. Methods: By using multi-stage sampling, a total of 26,688 students were successfully recruited from 29 senior high schools of a very large City in western China, Chongqing municipality. In this cross-sectional online survey, students' demographic and lifestyle characteristics were collected with a standardized questionnaire. The Young's IA Test, the Chinese Six-item QOL questionnaire, and item 15 of the Symptom Checklist-90-R were used to measure IA, QOL, and SI, respectively. Results: The 1-month prevalence of SI was 11.5% among students of senior high schools in Chongqing, China. Students with SI had significantly higher QOL scores (17.3 ± 3.7 vs. 13.7 ± 3.8, P < 0.001) and higher prevalence of IA (49.6% vs. 25.6%, P < 0.001) than those without SI. After controlling for demographic, lifestyle, and clinical covariates, IA (odd ratio (OR) = 1.15, P = 0.003) and a high QOL score (OR = 1.09, P < 0.001) remained significantly associated with SI. Conclusion: Suicidal ideation is prevalent among Chinese adolescents and it is associated with IA and poor QOL. Measures aimed at reducing IA and improving QOL may help prevent suicidal behaviors among Chinese adolescents.

3.
Ecol Evol ; 9(12): 7057-7068, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31380033

RESUMO

Although domestication has dramatically altered the phenotype, physiology, and life history of ramie (Boehmeria nivea) plants, few studies have investigated the effects of domestication on the structure and expression pattern of genes in this fiber crop. To investigate the selective pattern and genetic relationships among a cultivated variety of ramie (BNZ: B. nivea, ZZ1) and four wild species, BNT (B. nivea var. tenacissima), BNN (B. nivea var. nipononivea), BNW (B. nivea var. nivea), and BAN (B. nivea var. viridula), in the section Tilocnide, we performed an RNA sequencing analysis of these ramie species. The de novo assembly of the "all-ramie" transcriptome yielded 119,114 unigenes with an average length of 633 bp, and a total of 7,084 orthologous gene pairs were identified. The phylogenetic tree showed that the cultivar BNZ clustered with BAN in one group, BNW was closely related to BNT, and BNN formed a separate group. Introgression analysis indicated that gene flow occurred from BNZ to BNN and BAN, and between BAN and BNN. Among these orthologs, 2,425 and 269 genes underwent significant purifying and positive selection, respectively. For these positively selected genes, oxidation-reduction process (GO:0055114) and stress response pathways (GO:0006950) were enriched, indicating that modulation of the cellular redox status was important during both ramie fiber evolution and improvement. Two genes related to the suppression of flowering and one gene annotated as a flowering-promoting factor were subjected to positive selection, probably caused by human manipulation. Additionally, five genes were homologs of those involved in abiotic stress tolerance and disease resistance, with higher expression levels in the cultivar BNZ than in the wild species. Collectively, the results of this study indicated that domestication has resulted in the upregulation of many genes involved in the abiotic and biotic stress responses, fiber yield, and plant growth of ramie.

4.
Neuropharmacology ; 155: 31-43, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31103617

RESUMO

Ghrelin is an orexigenic hormone that also plays an important role in mood disorders. Our previous studies demonstrated that ghrelin administration could protect against depression-like behaviors of chronic unpredictable mild stress (CUMS) in rodents. However, the mechanism related to the effect of ghrelin on CUMS mice has yet to be revealed. This article shows that ghrelin (5 nmol/kg/day for 2 weeks, i.p.) decreased depression-like behaviors induced by CUMS and increased hippocampal integrity (neurogenesis and spine density) measured via Ki67, 5-bromo-2-deoxyuridine (BrdU), doublecortin (DCX) labeling and Golgi-cox staining, which were decreased under CUMS. The behavioral phenotypes of Growth hormone secretagogue receptor (Ghsr)-null and wild type (WT) mice were evaluated under no stress condition and after CUMS exposure to determine the effect of Ghsr knockout on the behavioral phenotypes and stress susceptibility of mice. Ghsr-null mice exhibited depression-like behaviors under no stress condition. CUMS induced similar depression- and anxiety-like behavioral manifestations in both Ghsr-null and WT mice. A similar pattern of behavioral changes was observed after hippocampal GHSR knockdown. Additionally, both Ghsr knockout as well as CUMS exhibited deleterious effects on neurogenesis and spine density in the dentate gyrus (DG). Besides, CCK8 assay and 5-Ethynyl-2'-deoxyuridine (EdU) incorporation assay showed that ghrelin has a proliferative effect on primary cultured hippocampal neural stem cells (NSCs) and this proliferation was blocked by D-Lys3-GHRP-6 (DLS, the antagonist of GHSR, 100 µM) pretreatment. Ghrelin-induced proliferation is associated with the inhibition of G1 arrest, and this inhibition was blocked by LY294002 (specific inhibitor of PI3K, 20 µM). Furthermore, the in vivo data displayed that LY294002 (50 nmol, i.c.v.) can significantly block the antidepressant-like action of exogenous ghrelin treatment. All these results suggest that ghrelin/GHSR signaling maintains the integrity of hippocampus and has an inherent neuroprotective effect whether facing stress or not.


Assuntos
Grelina/deficiência , Hipocampo/metabolismo , Neurogênese/fisiologia , Fármacos Neuroprotetores/metabolismo , Receptores de Grelina/deficiência , Estresse Psicológico/metabolismo , Animais , Células Cultivadas , Cromonas/farmacologia , Doença Crônica , Grelina/genética , Hipocampo/citologia , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Morfolinas/farmacologia , Neurogênese/efeitos dos fármacos , Receptores de Grelina/antagonistas & inibidores , Receptores de Grelina/genética , Estresse Psicológico/prevenção & controle , Estresse Psicológico/psicologia
5.
Sci Rep ; 9(1): 7913, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31113997

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30853341

RESUMO

Ghrelin, a peptide derived from stomach, is an endogenous ligand for growth hormone secretagogue receptor (GHSR). So far, the exact role of ghrelin in depression and anxiety is still being debated. The p38 mitogen-activated protein kinase (p38-MAPK) is known to be activated in response to various stress stimuli. Thus, we hypothesize that ghrelin has an antidepressant effect, to which the p38-MAPK signaling pathway significantly contributes. To test this hypothesis, chronic social defeat stress (CSDS) was used as a model of depression. We employed the adeno-associated virus-mediated siRNA approach to down-regulate GHSR expression in the hippocampus of mice in vivo. Both ghrelin and the p38 inhibitor, SB203580, were administered to identify the effect of ghrelin on depressive-like behavior of stressed mice and to better assess the role of the p38-MAPK signaling pathway in this process. We found that CSDS activated the endogenous ghrelin-GHSR in hippocampal neurons, which possibly resulted in opposing the formation of depression- and anxiety-like behaviors in mice. Furthermore, the p38-MAPK signaling pathway had an important role in the antidepressant effect of ghrelin. Therefore, we conclude that ghrelin may reduce CSDS-induced depression- and anxiety-like behaviors via inhibiting the p38-MAPK signaling pathway in hippocampal neurons of mice.


Assuntos
Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Grelina/farmacologia , Hipocampo/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Hipocampo/metabolismo , Imidazóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piridinas/farmacologia
7.
Sci Rep ; 9(1): 1134, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718553

RESUMO

The aim of this study is to access influences of scan-position on clinical ultra-high-resolution CT scanning. We proposed a breath-hold assisted ultra-high-resolution scanning technology (scan scheme G) and compared with scan scheme A (regular CT plain scan) and scheme B (1024 ultra-high-resolution scan with patients stay in supine position). A total of 30 patients with fGGO were included in this study. Three highly experienced chest imaging doctors were employed to score the image and to select regions of interest (ROIs) for CT value and signal-to-noise ratio (SNR) calculation. In comparison with scan A and B, this new scan scheme G shows more clear CT images and higher SNRs at overall lung field (the p-values of A versus G and B versus G are 0.041 and 0.065, respectively). These findings suggest that scan-G provides a better image quality and contributes significantly to clinical detection accuracy of fGGO.

8.
J Psychiatr Res ; 111: 51-58, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30677645

RESUMO

We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of antipsychotics to augment serotonin reuptake inhibitors (SRIs) for treatment-resistant obsessive-compulsive disorder (OCD) in adults. PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched on September 8, 2018. Randomized controlled trials investigating antipsychotics as augmentation agents were included. Network meta-analyses were performed using frequentist methods. Efficacy was measured by the Yale-Brown Obsessive-Compulsive Scale. Tolerability was measured by side-effect discontinuations. Mean differences (MDs) and odds ratios (ORs) were reported with 95% confidence intervals (CIs). Twenty articles with 790 patients were included. Our analyses showed that there was no significant difference in efficacy between antipsychotic agents. The order of efficacy rankings was inconsistent between primary analysis and sensitivity analyses. We found that there was considerable heterogeneity between studies. Comorbid tics was identified as a significant moderator. All antipsychotics except paliperidone were significantly superior to placebo in the subgroup without comorbid tics, while no antipsychotics was significantly superior to placebo in the comorbid tics subgroup. With respect to tolerability, quetiapine (OR, 3.45; 95% CI, 1.04-11.11) and paliperidone (20.00; 1.01->100) were significantly less tolerable than placebo. Based on this network meta-analysis, antipsychotic agents as augmentations to SRIs might be more effective in treatment-resistant OCD patients without comorbid tics. Definitive determination of which drug is optimal cannot be drawn currently because of the limited numbers of studies and heterogeneity across studies.

9.
J Hum Hypertens ; 33(6): 466-474, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30647461

RESUMO

A series of guidelines concerning hypertension emphasize the importance of follow-up in patients' management. The aim of this study was to assess the impact of routine follow-up on blood pressure (BP) control. A total of 1511 patients with hypertension aged ≥ 35 years were selected randomly from 17 communities in two cities and four townships located in Shandong and Jiangsu provinces in China. About half of the patients visited the community clinic four or more times yearly; follow-up was conducted by telephone for 43.3%. Forty-four point two percent of patients who did not visit a community clinic received telephonic follow-up; a higher percentage of telephonic follow-up was found in patients who visited community clinics frequently. Positive changes in BP level and BP control were associated with the number of clinical visits, while no significant correlations were found with telephonic follow-up. After adjustment for covariates, a higher number of clinic visits was associated with better BP control, with odds ratios of 1.628 (95% confidence interval (CI): 1.141-2.322), 1.472 (95% CI: 1.008-2.271), and 1.790 (95% CI: 1.154-2.778) for 4-6, 7-12, and >12 visits/year, respectively. Taking an antihypertensive drug showed a strong, positive association with the number of clinic visits (OR 1.747, 95% CI: 1.484-2.056). These data suggest that health care systems may achieve greater success by increasing the frequency of clinical visits and that the positive changes may be related to improvement in medication adherence. Routine follow-up by telephone was not significantly associated with BP level and BP control.

10.
Behav Brain Res ; 359: 845-852, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30041006

RESUMO

Postmenopausal depression has been shown to be related to the reduction of ovarian hormones produced as a woman transitions from a menopausal to a post-menopausal stage. What remains to be known is which type of estrogen receptor plays a key role in estrogen neuroprotection, a process that may be mediated by potentiating brain mitochondrial function and inhibiting mitochondria-associated apoptosis. In order to better imitate the condition of postmenopause, we conducted our research on aged female rats. Plasma estrogen levels declined significantly in ovariectomized rats and 16-month-old female rats, while anxiety and depression-like behavior increase. Moreover, ERα, ERß, GPER, Bcl2 and UCP2 expression decreased significantly in hippocampus in female rats following ovariectomy. In our study, the anxiety and depression-like behavior in aged female rats were significantly relieved after the treatment of G-1, the GPER agonist. Furthermore, G-1 could reverse the reduction of ERα, ERß, GPER, Bcl2 and UCP2 expression within the hippocampus. Mitochondrial JC-1 staining indicated that mitochondrial membrane potential increased after G-1 treatment. In addition, total antioxidant capacity (TAC) and superoxide dismutase activity (SOD) were found to be elevated in aged female rats following G-1 treatment. Taken together, estrogen receptors, especially GPER, may activate anti-apoptotic signaling and accelerate mitochondrial function. Therefore, GPER could be the potential therapeutic target for estrogen deficiency-related affective disorders.


Assuntos
Envelhecimento/efeitos dos fármacos , Ciclopentanos/farmacologia , Hipocampo/efeitos dos fármacos , Transtornos do Humor/tratamento farmacológico , Oxirredução/efeitos dos fármacos , Quinolinas/farmacologia , Receptores Estrogênicos/metabolismo , Animais , Modelos Animais de Doenças , Estrogênios/sangue , Comportamento Exploratório/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/ultraestrutura , Aprendizagem em Labirinto/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Natação/psicologia
11.
Physiol Plant ; 167(4): 564-584, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30561011

RESUMO

Abrupt drought-flood alternation (T1) is a meteorological disaster that frequently occurs during summer in southern China and the Yangtze river basin, often causing a significant loss of rice production. In this study, the response mechanism of yield decline under abrupt drought-flood alternation stress at the panicle differentiation stage was analyzed by looking at the metabolome, proteome as well as yield and physiological and biochemical indexes. The results showed that drought and flood stress caused a decrease in the yield of rice at the panicle differentiation stage, and abrupt drought-flood alternation stress created a synergistic effect for the reduction of yield. The main reason for the decrease of yield per plant under abrupt drought-flood alternation was the decrease of seed setting rate. Compared with CK0 (no drought and no flood), the net photosynthetic rate and soluble sugar content of T1 decreased significantly and its hydrogen peroxidase, superoxide dismutase, peroxidase activity increased significantly. The identified differential metabolites and differentially expressed proteins indicated that photosynthesis metabolism, energy metabolism pathway and reactive oxygen species response have changed strongly under abrupt drought-flood alteration stress, which are factors that leads to the rice grain yield reduction.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30576763

RESUMO

BACKGROUND: Various agents for augmentation of serotonin reuptake inhibitors have been investigated for treatment-resistant obsessive-compulsive disorder (OCD). We aimed to comprehensively compare different augmentation agents for treatment-resistant OCD in adults. METHODS: PubMed, Embase, Web of Science, CENTRAL, the WHO's ICTRP, and ClinicalTrials.gov were searched on February 20, 2018. Pairwise meta-analysis and Bayesian network meta-analysis were performed. The primary outcome was efficacy measured by the Yale-Brown Obsessive Compulsive Scale. The secondary outcomes were tolerability (side-effect discontinuation) and acceptability (all cause discontinuation). Mean differences (MDs) and odds ratios (ORs) were reported with 95% confidence intervals (CIs). RESULTS: Thirty-three articles with 34 trials (1216 patients) were included. Memantine (MD, -8.94; 95% CI, -14.42 to -3.42), risperidone (-4.47, -8.75 to -0.17), topiramate (-6.05, -10.89 to -1.20), lamotrigine (-6.07, -11.61 to -0.50), and aripiprazole (-5.14, -9.95 to -0.28) were significantly superior to placebo. Antipsychotic (-4.09, -6.22 to -1.93) and glutamatergic (-5.22, -7.53 to -2.84) agents were significantly superior to placebo. Considerable heterogeneity was found across studies, and baseline symptom severity was identified as a significant moderator. After baseline severity adjustment, quetiapine (-5.00, -8.59 to -1.29) and olanzapine (-8.28, -15.34 to -1.13) became significantly superior to placebo. CONCLUSIONS: Our study supports the use of antipsychotic or glutamatergic agents as augmentation agents for treatment-resistant OCD. Topiramate, lamotrigine, aripiprazole, olanzapine, risperidone, memantine, and quetiapine are alternative augmentation drugs; however, a definitive conclusion of the best drug remains undetermined because of the considerable heterogeneity and limited numbers of studies and patients for each agent.


Assuntos
Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Psicotrópicos/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Resistência a Medicamentos , Quimioterapia Combinada , Humanos , Metanálise em Rede
13.
Ying Yong Sheng Tai Xue Bao ; 29(8): 2566-2574, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30182596

RESUMO

Four levels of nitrogen application (N1, low nitrogen, 90 kg N·hm-2; N2, normal nitrogen, 180 kg N·hm-2; N3, high nitrogen, 250 kg N·hm-2; N4, ultra high nitrogen, 330 kg N·hm-2) were set to examine the effects of nitrogen application on the growth and development, yield formation and related physiological characteristics of late rice under low temperature condition during heading and flowering stage, with super hybrid late rice variety Wufengyou T025 as test material. The results showed that yield of all treatments decreased in different degrees under the low temperature conditions, with the yield of N2 being the highest, and N1 the lowest. The effective panicles per plant and total grains per panicle in N3 and N4 were higher than those of the other treatments, but their seed setting rate and harvest index were significantly decreased. With the increases of nitrogen application rates, pocketed panicle rate, the total dry mass and chlorophyll contents (SPAD value) increased to different extent, while the panicle dry mass of N2 was the highest. After low temperature, chlorophyll content, net photosynthetic rate and transpiration rate of the total treatments decreased to varying degrees, and the declined range of the net photosynthetic rate and trans-piration rate in N3 and N4 were higher than other treatments. The contents of free proline, malondialdehyde and peroxidase activity of all treatments increased to varying extent, while superoxide dismutase, catalyes activities and the soluble protein contents decreased, with the magnitude of variation in N3 and N4 being the greatest. It demonstrated that high amounts of nitrogen application were unfavorable to late rice to resist low temperature at heading and flowering stage and thus misuse of nitrogen fertilizer application should be avoided in production. The suitable amount of nitrogen application in double cropping late rice was not more than 180 kg·hm-2.


Assuntos
Oryza , Clorofila , Temperatura Baixa , Fertilizantes , Nitrogênio , Fotossíntese , Temperatura
14.
Brain Struct Funct ; 223(2): 609-618, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28900727

RESUMO

Ubiquitin-like with PHD and ring finger domains 2 (Uhrf2) is distributed in many brain regions, including the cortex and hippocampus. Decreased Uhrf2 expression is involved in neurodegenerative disease. A recent study showed Uhrf2 deletion impaired spatial memory; however, the mechanism remains elusive. In our study, we determined that Uhrf2+/- and Uhrf2-/- mice had significant learning and memory deficiencies in contextual fear conditioning (CFC) and the novel place recognition test but not in the novel object recognition test. Interestingly, there were no changes in the Uhrf2 protein levels in the hippocampus of C57BL6 mice after CFC training, which suggests Uhrf2 in adult mice may not be related to the formation of CFC long-term memory. Based on Nissl staining, Uhrf2 deletion caused neuropathological changes specifically in the crest of the dentate gyrus (DG), such as cell swelling, a vague outline and confused boundary; however, no changes were identified in the medial prefrontal cortex (mPFC). Transmission electron microscope assay further indicated a series of abnormal ultrastructure changes in neurons and glia in the DG crest. These results suggested that Uhrf2 deletion selectively blocked the development of the DG crest and impaired hippocampus-dependent learning and memory. Our study will facilitate a better understanding of the role of Uhrf2 protein in the central nervous system.


Assuntos
Giro Denteado/patologia , Transtornos da Memória/genética , Transtornos da Memória/patologia , Ubiquitina-Proteína Ligases/deficiência , Animais , Condicionamento Clássico/fisiologia , Giro Denteado/ultraestrutura , Modelos Animais de Doenças , Comportamento Exploratório/fisiologia , Medo/psicologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia Eletrônica , Aprendizagem Espacial/fisiologia , Ubiquitina-Proteína Ligases/genética
15.
Medicine (Baltimore) ; 96(45): e8515, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29137053

RESUMO

BACKGROUND: Ischemic stroke (IS) is a devastating occurrence affecting millions worldwide. This study aimed to evaluate the prognostic value of high-resolution magnetic resonance imaging (HRMRI) in assessing carotid atherosclerotic plaque in IS patients. METHODS: Between January 2013 and March 2015, 338 IS patients were recruited for the investigative purposes of the study. All participants of the study underwent an HRMRI inspection procedure after being admitted into the hospital. During this study, we systematically analyzed and measured various types of fibrous caps, lipid compositions, and plaque lipid ratios. Univariate and multivariate logistic regression analyses were performed for predicting prognosis of IS patients. A receiver-operating characteristic (ROC) curve was employed to determine the accuracy of the IS prognosis. RESULTS: The percentage of type I fibrous caps exhibited significant decrease, while the percentage of type III fibrous caps, lipid compositions, and lipid ratios all displayed increase. The results of the univariate analysis indicated that age, hypertension, hyperlipidemia, treatment regimens, fibrous cap type, plaque type, lipid composition, and lipid ratio shared a correlation in regards to the poor prognosis of IS patients. Multivariate logistic regression analysis demonstrated that the prognosis of IS patients was not necessarily dependent on fibrous cap type, plaque type, or age. ROC curves revealed that the HRMRI possessed a strong predicative ability in relation to the identification of the prognosis of IS patients through factors such as type of plaque and fibrous caps determination. CONCLUSION: Our study conclusively intimated the promise of HRMRI as an evaluative tool for the determination of carotid atherosclerotic plaques in patients with IS.


Assuntos
Doenças das Artérias Carótidas/patologia , Imagem por Ressonância Magnética/métodos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Acidente Vascular Cerebral/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Lipídeos/análise , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/epidemiologia , Prognóstico , Curva ROC
16.
Cell Death Dis ; 8(8): e3008, 2017 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-28837146

RESUMO

The limited efficacy of current treatment methods and increased type 2 diabetes mellitus (T2DM) incidence constitute an incentive for investigating how metabolic homeostasis is maintained, to improve treatment efficacy and identify novel treatment methods. We analyzed a three-generation family of Chinese origin with the common feature of T2DM attacks and fatty pancreas (FP), alongside 19 unrelated patients with FP and 58 cases with T2DM for genetic variations in Enho, serum adropin, and relative Treg amounts. Functional studies with adropin knockout (AdrKO) in C57BL/6J mice were also performed. It showed serum adropin levels were significantly lower in FP and T2DM patients than in healthy subjects; relative Treg amounts were also significantly decreased in FP and T2DM patients, and positively associated with adropin (r=0.7220, P=0.0001). Sequencing revealed that the patients shared a Cys56Trp mutation in Enho. In vivo, adropin-deficiency was associated with increased severity of glucose homeostasis impairment and fat metabolism disorder. AdrKO mice exhibited reduced endothelial nitric oxide synthase (eNOS) phosphorylation (Ser1177), impaired glycosphingolipid biosynthesis, adipocytes infiltrating, and loss of Treg, and developed FP and T2DM. Adropin-deficiency contributed to loss of Treg and the development of FP disease and T2DM.


Assuntos
Proteínas Sanguíneas/deficiência , Diabetes Mellitus Tipo 2/terapia , Dieta Hiperlipídica/efeitos adversos , Obesidade/complicações , Pâncreas/patologia , Peptídeos/deficiência , Animais , Diabetes Mellitus Tipo 2/patologia , Feminino , Homeostase , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Obesidade/patologia
17.
J Neurosci ; 37(25): 5978-5995, 2017 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-28500221

RESUMO

Multiple studies have established that brain-derived neurotrophic factor (BDNF) plays a critical role in the regulation of synaptic plasticity via its receptor, TrkB. In addition to being phosphorylated, TrkB has also been demonstrated to be ubiquitinated. However, the mechanisms of TrkB ubiquitination and its biological functions remain poorly understood. In this study, we demonstrate that ubiquitin C-terminal hydrolase L1 (UCH-L1) promotes contextual fear conditioning learning and memory via the regulation of ubiquitination of TrkB. We provide evidence that UCH-L1 can deubiquitinate TrkB directly. K460 in the juxtamembane domain of TrkB is the primary ubiquitination site and is regulated by UCH-L1. By using a peptide that competitively inhibits the association between UCH-L1 and TrkB, we show that the blockade of UCH-L1-regulated TrkB deubiquitination leads to increased BDNF-induced TrkB internalization and consequently directs the internalized TrkB to the degradation pathway, resulting in increased degradation of surface TrkB and attenuation of TrkB activation and its downstream signaling pathways. Moreover, injection of the peptide into the DG region of mice impairs hippocampus-dependent memory. Together, our results suggest that the ubiquitination of TrkB is a mechanism that controls its downstream signaling pathways via the regulation of its endocytosis and postendocytic trafficking and that UCH-L1 mediates the deubiquitination of TrkB and could be a potential target for the modulation of hippocampus-dependent memory.SIGNIFICANCE STATEMENT Ubiquitin C-terminal hydrolase L1 (UCH-L1) has been demonstrated to play important roles in the regulation of synaptic plasticity and learning and memory. TrkB, the receptor for brain-derived neurotrophic factor, has also been shown to be a potent regulator of synaptic plasticity. In this study, we demonstrate that UCH-L1 functions as a deubiquitinase for TrkB. The blockage of UCH-L1-regulated deubiquitination of TrkB eventually results in the increased degradation of surface TrkB and decreased activation of TrkB and its downstream signaling pathways. In vivo, UCH-L1-regulated TrkB deubiquitination is necessary for hippocampus-dependent memory. Overall, our study provides novel insights into the mechanisms of UCH-L1-mediated neurobiological functions and suggests that ubiquitination is an important regulatory signal for TrkB functions.


Assuntos
Hipocampo/fisiologia , Memória/fisiologia , Receptor trkB/metabolismo , Ubiquitina Tiolesterase/metabolismo , Ubiquitinação/fisiologia , Animais , Azepinas/farmacologia , Benzamidas/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Condicionamento Operante/fisiologia , Endocitose/genética , Endocitose/fisiologia , Medo/psicologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Atividade Motora/genética , Atividade Motora/fisiologia , Neurônios/metabolismo , Receptor trkB/antagonistas & inibidores , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Ubiquitina Tiolesterase/genética , Ubiquitinação/genética
18.
Biomed Environ Sci ; 30(3): 157-169, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28427485

RESUMO

OBJECTIVE: To examine the association between habitual sleep duration and obesity among Chinese adults. METHODS: The association of sleep duration and obesity was investigated among 7,094 community-dwelling Chinese adults. Sleep duration was self-reported. In this study, obesity was defined as follows: body mass index (BMI) ⋝ 28 kg/m2, waist circumference (WC) ⋝ 85 cm in men and ⋝ 80 cm in women, and percent body fat (%BF) ⋝ 25 in men and ⋝ 35 in women. Logistic and quantile regressions were employed to examine relationships of interest. RESULTS: Overall, 6.42% of the participants reported short sleep durations (< 6 h/d) while 14.71% reported long (⋝ 9 h/d) sleep durations. Long sleepers (⋝ 9 h/d) represented a greater frequency of women with obesity [odds ratio (OR): 1.30; 95% confidence interval (CI), 1.02-1.67] and high body fat (1.43, 1.04-1.96) than those who slept 7-8 h/d. An association between long sleep times and higher BMI estimations was found across the 10th-75th percentile of the BMI distribution. Among men, long sleepers (⋝ 9 h/d) presented lower risks of developing abdominal obesity compared with individuals who slept 7-8 h/d (OR = 0.79, 95% CI: 0.44-0.99). CONCLUSION: Our study suggests that long sleep durations are associated with general obesity in Chinese women but reduced waist circumferences in men. Confirmatory studies are needed to determine the heterogeneous association of sleep time and obesity by gender.


Assuntos
Tecido Adiposo/fisiologia , Grupo com Ancestrais do Continente Asiático , Índice de Massa Corporal , Sono/fisiologia , Circunferência da Cintura , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População Rural , Inquéritos e Questionários , População Urbana
19.
J Neurosci ; 37(14): 3848-3863, 2017 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-28283560

RESUMO

Histone acetylation, an epigenetic modification, plays an important role in long-term memory formation. Recently, histone deacetylase (HDAC) inhibitors were demonstrated to promote memory formation, which raises the intriguing possibility that they may be used to rescue memory deficits. However, additional research is necessary to clarify the roles of individual HDACs in memory. In this study, we demonstrated that HDAC7, within the dorsal hippocampus of C57BL6J mice, had a late and persistent decrease after contextual fear conditioning (CFC) training (4-24 h), which was involved in long-term CFC memory formation. We also showed that HDAC7 decreased via ubiquitin-dependent degradation. CBX4 was one of the HDAC7 E3 ligases involved in this process. Nur77, as one of the target genes of HDAC7, increased 6-24 h after CFC training and, accordingly, modulated the formation of CFC memory. Finally, HDAC7 was involved in the formation of other hippocampal-dependent memories, including the Morris water maze and object location test. The current findings facilitate an understanding of the molecular and cellular mechanisms of HDAC7 in the regulation of hippocampal-dependent memory.SIGNIFICANCE STATEMENT The current findings demonstrated the effects of histone deacetylase 7 (HDAC7) on hippocampal-dependent memories. Moreover, we determined the mechanism of decreased HDAC7 in contextual fear conditioning (CFC) through ubiquitin-dependent protein degradation. We also verified that CBX4 was one of the HDAC7 E3 ligases. Finally, we demonstrated that Nur77, as one of the important targets for HDAC7, was involved in CFC memory formation. All of these proteins, including HDAC7, CBX4, and Nur77, could be potential therapeutic targets for preventing memory deficits in aging and neurological diseases.


Assuntos
Medo/fisiologia , Histona Desacetilases/metabolismo , Ligases/metabolismo , Memória/fisiologia , Complexo Repressor Polycomb 1/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação/fisiologia , Animais , Medo/psicologia , Células HEK293 , Hipocampo/metabolismo , Humanos , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL
20.
Ying Yong Sheng Tai Xue Bao ; 28(11): 3562-3570, 2017 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-29692099

RESUMO

Super hybrid early rice variety Ganxin 203 was used as test material, and four foliar spraying treatments were set using clear water as the control group (CK), and 3 concentrations of potassium dihydrogen phosphate (KH2PO4) with 0.1% (P1), 0.3% (P3), 0.5% (P5) and po-tash (MH). The effects of spraying P and K fertilizers on the leaf temperature, yield and physiolo-gical characteristics in double-season early rice under low temperature conditions during panicle primordium differentiation stage were studied. The results showed that during the low temperature period 6:00-18:00, rice leaf temperature under the different treatments with potassium dihydrogen phosphate and potash was higher than that of CK. Leaf chlorophyll content and net photosynthetic rate (Pn) of rice plants decreased gradually with the treatments under low temperature, while the reduction range was the smallest in treatment P3. The activities of the antioxidative enzymes varied to different extents, and the increase range for the activities of superoxide dismutase (SOD) and peroxidase (POD) in treatment P3 were higher than those in the other treatments. The decrease range of the activity catalase (CAT) in treatment P3 was lower than that in the other treatments. At the end of low temperature treatment, malondialdehyde (MDA) content was the highest in CK. Under low temperature, foliar spraying of potassium dihydrogen phosphate or potash could improve dry matter accumulation to varying degrees and achieve the purpose of slowing down the yield decrease, among which treatment P3 was the best. It could be found from the yield components that the total grains per panicle, seed setting rate and 1000-grain mass were significantly improved for all treatments compared to CK. The application of foliar spraying of 0.3% potassium dihydrogen phosphate was the most effective agronomic measure to enhance the resistance to low temperature during panicle primordium differentiation stage for double-season super hybrid early rice.


Assuntos
Fertilizantes , Oryza , Temperatura Baixa , Fotossíntese , Folhas de Planta
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