Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 58
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Mol Cell Endocrinol ; 501: 110660, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31759099

RESUMO

The bioactive lipid mediator sphingosine 1-phosphate (S1P) is considered to be involved in the development of insulin resistance (IR) via effects on oxidative stress; the mechanism however is not yet fully revealed. To this end, we investigated the role and mechanism of S1P on hepatic IR. We found that treatment of the normal human liver cell LO2 with 1000 nM insulin for 48 h reduced glucose uptake and increased serine phosphorylation of insulin receptor substrate-1, indicating a reduction in insulin receptor signaling. Moreover, the same concentration of insulin caused accumulation of reactive oxygen species (ROS) in the cytosol and mitochondria, and enhanced expression of the antioxidant transcription factor (Nrf2) and upregulated Nrf2 nuclear translocation. Using known inhibitors and donors of ROS (H2O2, ·O2-, ·OH), the results demonstrated the differential roles for the specific ROS in regulating IR in LO2 cells, with H2O2 having a more significant inhibitory role compared with ·O2- and ·OH. Cell treatment with S1P at 0.1-5.0 µM reversed the effects of high insulin concentrations on ROS generation, glucose uptake, and insulin signaling. H2O2 also reversed the beneficial effects of S1P in alleviating IR. These results show that H2O2 signaling plays a key determinant in hepatic IR induced by insulin. S1P can ameliorate hepatic IR by reducing mitochondrial ROS generation, and the possible anti-IR effect mechanism may be involved in H2O2 signaling.

2.
Int J Chron Obstruct Pulmon Dis ; 14: 2103-2115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564857

RESUMO

Introduction: Chronic obstructive pulmonary disease (COPD) is a lung disease closely related to exposure to exogenous substances. CYP2B6 can activate many exogenous substances, which in turn affect lung cells. The aim of this study was to assess the association of single-nucleotide polymorphisms (SNPs) in CYP2B6 with COPD risk in a Chinese Han population. Materials and methods: Genotypes of the five candidate SNPs in CYP2B6 were identified among 318 cases and 508 healthy controls with an Agena MassARRAY method. The association between CYP2B6 polymorphisms and COPD risk was evaluated using genetic models and haplotype analyses. Results: In allele model, we observed that rs4803420 G and rs1038376 A were related to COPD risk. And rs4803420 G/T and G/T-T/T were related to a decreased COPD risk compared to GG genotype in the co-dominant and dominant models, respectively. When comparing with the AA genotype, rs1038376 A/T and A/T-T/T were associated with an increased COPD risk in the co-dominant and dominant models, respectively. Further gender stratification co-dominant and dominant models analysis showed that genotype G/T and G/T-T/T of rs4803420, and genotype A/T and A/T-T/T of rs1038376 were significantly associated with COPD risk compared to the wide type in males and females, while allele C of rs12979270 was only associated with COPD risk in females. Smoking status stratification analysis showed that rs12979270 C was significantly associated with an increased COPD risk under the allele model compared with allele A in the smoking subgroup. Haplotype analysis showed that haplotype GTA and TAA were related to COPD risk. Conclusion: Our data is the first to demonstrate that CYP2B6 polymorphisms may exert effects on COPD susceptibility in the Chinese Han population.

3.
J Surg Oncol ; 120(4): 685-697, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31317558

RESUMO

BACKGROUND: How to best evaluate the disease-specific survival (DSS) of gastric cancer (GC) survivors over time is unclear. METHODS: Clinicopathological data from 22 265 patients who underwent curative intend resection for GC were retrospectively analyzed. Changes in the patients' 3-year conditional disease-specific survival (CS3) were analyzed. We used time-dependent Cox regression to analyze which variables had long-term effects on DSS and devised a dynamic predictive model based on the length of survival. RESULTS: Based on 1-, 3-, and 5-year survivorships, the CS3 of the population increased gradually from 62% to 68.1%, 83.7%, and 90.6%, respectively. Subgroup analysis showed that the CS3 of patients who had poor prognostic factors initially demonstrated the greatest increase in postoperative survival time (eg, N3b: 26.6%-84.1%, Δ57.5% vs N0: 84.1%-93.3%, Δ9.2%). Time-dependent Cox regression analysis showed the following predictor variables constantly affecting DSS: age, the number of examined lymph nodes (LNs), T stage, N stage, and site (P < .05). These variables served as the basis for a dynamic prediction model. CONCLUSIONS: The influence of prognostic factors on DSS and CS3 changed dramatically over time. We developed an effective model for predicting the DSS of patients with GC based on the length of survival time.


Assuntos
Adenocarcinoma/mortalidade , Bases de Dados Factuais , Gastrectomia/mortalidade , Excisão de Linfonodo/mortalidade , Complicações Pós-Operatórias/mortalidade , Neoplasias Gástricas/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Feminino , Humanos , Agências Internacionais , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Taxa de Sobrevida
4.
Mol Genet Genomic Med ; 7(8): e773, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31270965

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide and is characterized by a partially reversible airflow limitation. Currently, many studies put forward that COPD is associated with both genetic and environmental factors. It has been reported that germline mutations in telomerase are risk factors for COPD susceptibility. In this study, we validated the association between TERT polymorphisms and COPD risk with a case-control study in the Chinese Li population. METHODS: A total of 279 COPD patients and 290 control individuals were recruited. We identified five single nucleotide polymorphisms (SNPs) in TERT that were associated with COPD. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in logistic regression models after adjusting for age and gender to assess the association. RESULTS: In the genetic model analysis, we found the "C/T-T/T" genotype of rs10069690 in TERT was associated with an increased COPD risk in the dominant model (p = 0.046); the rs2853677 in TERT was significantly associated with increased COPD risk based on the codominant model ("A/G" genotype, p = 0.033), dominant model (A/G-G/G genotype, p = 0.0091), and log-additive model (p = 0.023). The rs2853676 in TERT could increase the risk of COPD in the dominant model ("C/T-T/T" genotype, p = 0.026) and in the Log-additive model (p = 0.022). CONCLUSION: Our data shed new light on the association between TERT SNPs and COPD susceptibility in the Chinese Li population.

5.
BMC Neurol ; 19(1): 166, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315588

RESUMO

BACKGROUND: Acquired epileptiform opercular syndrome (AEOS) with electrical status epilepticus during sleep (ESES) may be recurrent and intractable. The real-time transcranial Doppler ultrasound-sleep-deprived video electroencephalogram (TCD-SDvEEG) can be used to observe the relationships among hemodynamic, electrophysiological, and clinical factors in a patient during therapy. This study reported the case of a healthy 5-year-old boy with AEOS. CASE PRESENTATION: The patient had initial seizures during sleep at the age of 1 year, with the left mouth pouting, left eye blinking and drooling for several seconds, and, sometimes, the left upper-limb flexion and head version to the left, lasting for 1-2 min. The combined antiepileptic drug regimens, including valproate, lamotrigine, and clonazepam, failed in the present case. Therefore, the add-on high-dose methylprednisolone therapy was provided. Also, the serial TCD-SDvEEG was used to monitor the dynamic changes before and after add-on steroid treatment. The results showed less than 15% variation in the range of blood flow fluctuation with spikes during non-rapid eye movement sleep after treatment. This was similar to the outcomes in healthy children and also accorded with the clinical improvements such as seizure control, drooling control, and language ability melioration. However, 95% of spike-wave index (SWI) was still maintained. The improvements in cerebral hemodynamics and clinical manifestations were faster and earlier than the SWI progression. CONCLUSIONS: The real-time TCD-SDvEEG was highly sensitive in detecting therapeutic changes. The findings might facilitate the understanding of the mechanisms underlying neurovascular coupling in patients with AEOS accompanied by ESES.


Assuntos
Eletroencefalografia/métodos , Transtornos do Sono-Vigília/diagnóstico , Estado Epiléptico/diagnóstico , Anticonvulsivantes/uso terapêutico , Pré-Escolar , Humanos , Masculino , Metilprednisolona/uso terapêutico , Convulsões/tratamento farmacológico , Sono/fisiologia , Transtornos do Sono-Vigília/fisiopatologia , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/fisiopatologia , Síndrome , Falha de Tratamento , Ultrassonografia Doppler Transcraniana , Ácido Valproico/uso terapêutico
6.
Autophagy ; : 1-18, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31223056

RESUMO

Macroautophagy/autophagy deficit induces intracellular MAPT/tau accumulation, the hallmark pathology in Alzheimer disease (AD) and other tauopathies; however, the reverse role of MAPT accumulation in autophagy and neurodegeneration is not clear. Here, we found that overexpression of human wild-type full-length MAPT, which models MAPT pathologies as seen in sporadic AD patients, induced autophagy deficits via repression of autophagosome-lysosome fusion leading to significantly increased LC3 (microtubule-associated protein 1 light chain 3)-II and SQSTM1/p62 (sequestosome 1) protein levels with autophagosome accumulation. At the molecular level, intracellular MAPT aggregation inhibited expression of IST1 (IST1 factor associated with ESCRT-III), a positive modulator for the formation of ESCRT (the Endosomal Sorting Complex Required for Transport) complex that is required for autophagosome-lysosome fusion. Upregulating IST1 in human MAPT transgenic mice attenuated autophagy deficit with reduced MAPT aggregation and ameliorated synaptic plasticity and cognitive functions, while downregulating IST1 per se induced autophagy deficit with impaired synapse and cognitive function in naïve mice. IST1 can facilitate association of CHMP2B (charged multivesicular body protein 2B) and CHMP4B/SNF7-2 to form ESCRT-III complex, while lack of IST1 impeded the complex formation. Finally, we demonstrate that MAPT accumulation suppresses IST1 transcription with the mechanisms involving the ANP32A-regulated mask of histone acetylation. Our findings suggest that the AD-like MAPT accumulation can repress autophagosome-lysosome fusion by deregulating ANP32A-INHAT-IST1-ESCRT-III pathway, which also reveals a vicious cycle of MAPT accumulation and autophagy deficit in the chronic course of AD neurodegeneration.Abbreviations: AAV: adeno-associated virus; Aß: ß-amyloid; aCSF: artificial cerebrospinal fluid; AD: Alzheimer disease; ANP32A: acidic nuclear phosphoprotein 32 family member A; ATG: autophagy related; AVs: autophagic vacuoles; CEBPB: CCAAT enhancer binding protein beta; CHMP: charged multivesicular body protein; DMEM: Dulbecco's modified eagle's medium; EBSS: Earle's balanced salt solution; EGFR: epidermal growth factor receptor; ESCRT: endosomal sorting complex required for transport; fEPSPs: field excitatory postsynaptic potentials; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GSK3B: glycogen synthase kinase 3 beta; HAT: histone acetyl transferase; HDAC: histone deacetylase; INHAT: inhibitor of histone acetyl transferase; IST1: IST1 factor associated with ESCRT-III; LAMP2: lysosomal associated membrane protein 2; LTP: long-term potentiation; MAP1LC3: microtubule associated protein 1 light chain 3; MAPT/tau: microtubule associated protein tau; MVB: multivesicular bodies; MWM: Morris water maze; PBS: phosphate-buffered saline solution; RAB7: member RAS oncogene family; SNAREs: soluble N-ethylmaleimide-sensitive factor attachment protein receptors; SQSTM1/p62: sequestosome 1.

7.
EMBO Rep ; 20(6)2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31085626

RESUMO

Intracellular tau accumulation forming neurofibrillary tangles is hallmark pathology of Alzheimer's disease (AD), but how tau accumulation induces synapse impairment is elusive. By overexpressing human full-length wild-type tau (termed hTau) to mimic tau abnormality as seen in the brain of sporadic AD patients, we find that hTau accumulation activates JAK2 to phosphorylate STAT1 (signal transducer and activator of transcription 1) at Tyr701 leading to STAT1 dimerization, nuclear translocation, and its activation. STAT1 activation suppresses expression of N-methyl-D-aspartate receptors (NMDARs) through direct binding to the specific GAS element of GluN1, GluN2A, and GluN2B promoters, while knockdown of STAT1 by AAV-Cre in STAT1flox/flox mice or expressing dominant negative Y701F-STAT1 efficiently rescues hTau-induced suppression of NMDAR expression with amelioration of synaptic functions and memory performance. These findings indicate that hTau accumulation impairs synaptic plasticity through JAK2/STAT1-induced suppression of NMDAR expression, revealing a novel mechanism for hTau-associated synapse and memory deficits.

8.
Biochim Biophys Acta Mol Basis Dis ; 1865(6): 1477-1489, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30826466

RESUMO

BACKGROUND: Maternal immune activation (MIA) is an independent risk factor for psychiatric disorders including depression spectrum in the offsprings, but the molecular mechanism is unclear. Recent studies show that interferon-stimulated gene-15 (ISG15) is involved in inflammation and neuronal dendrite development; here we studied the role of ISG15 in MIA-induced depression and the underlying mechanisms. METHODS: By vena caudalis injecting polyinosinic: polycytidylic acid (poly I:C) into the pregnant rats to mimic MIA, we used AAV or lentivirus to introduce or silence ISG15 expression. Synaptic plasticity was detected by confocal microscope and Golgi staining. Cognitive performances of the offspring were measured by Open field, Forced swimming and Sucrose preference test. RESULTS: We found that MIA induced depression-like behaviors with dendrite impairments in the offspring with ISG15 level increased in the offsprings' brain. Overexpressing ISG15 in the prefrontal cortex of neonatal cubs (P0) could mimic dendritic pathology and depressive like behaviors, while downregulating ISG15 rescued these abnormalities in the offsprings. Further studies demonstrated that MIA-induced upregulation of inflammatory cytokines promoted ISG15 expression in the offspring' brain which suppressed Rap2A ubiquitination via NEDD4 and thus induced Rap2A accumulation, while upregulating NEDD4 abolished ISG15-induced dendrite impairments. CONCLUSIONS: These data reveal that MIA impedes offsprings' dendrite development and causes depressive like behaviors by upregulating ISG15 and suppressing NEDD4/Rap2A signaling. The current findings suggest that inhibiting ISG15 may be a promising intervention of MIA-induced psychiatric disorders in the offsprings.

9.
BMC Infect Dis ; 19(1): 292, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30925908

RESUMO

BACKGROUND: Syphilis is responsible for a substantial burden of preventable adverse outcomes in pregnancy. The purpose of this study was to compare the frequency of adverse pregnancy outcomes among syphilis-seropositive women who received different treatment regimens at different times in Guangzhou, China. METHODS: Pregnant women with syphilis infection who received prenatal and delivery services in Guangzhou between January 2014 and December 2016 were included. Association between treatment status and the composite adverse outcomes (preterm birth, infant smaller than gestational age, stillbirth, and spontaneous abortion) was estimated. RESULTS: Of 1187 syphilis-seropositive pregnant women included in the analysis, 900 (75.8%) syphilis-seropositive pregnant women received treatment, and 287(24.2%) did not receive treatment. Adverse pregnancy outcomes were observed among 16.3% (147/900) of women with treatment and 33.8% (97/287) of women without treatment. Syphilis-seropositive pregnant women treated with one or two courses of penicillin had a similar risk of adverse pregnancy outcomes (adjusted RR = 1.36, 95% CI: 0.94-1.96). Adverse outcomes were more common among women whose non-treponemal serum test titer was >1:8 and received treatment after 28 weeks compared to before 28 weeks (adjusted RR = 2.34, 95% CI: 1.22-4.48). CONCLUSIONS: Women who received one course of penicillin and women who received two courses of penicillin had a similar risk of adverse pregnancy outcomes. Syphilis treatment before 28 weeks of pregnancy is critical. Strategies to promote high-quality prenatal services are needed.


Assuntos
Complicações Infecciosas na Gravidez/microbiologia , Sífilis/tratamento farmacológico , Aborto Espontâneo/microbiologia , Adulto , Antibacterianos/uso terapêutico , China , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Penicilinas/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Nascimento Prematuro , Estudos Retrospectivos , Natimorto , Sífilis/prevenção & controle , Sífilis/transmissão
10.
Diabetes Obes Metab ; 2018 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-30471182

RESUMO

AIMS: To investigate the prevalence of adult-onset autoimmune diabetes (ADM) and predisposition to autoimmune diseases by quantifying serum organ-specific autoantibodies in people with phenotype of type 2 diabetes (T2D). MATERIALS AND METHODS: We included a nationally representative sample of 46 239 adults aged ≥20 years from 14 provinces, of whom 4671 had diabetes, plus 1000 control subjects with normal glucose tolerance (NGT). Participants were screened centrally for autoantibodies to glutamic acid decarboxylase (GAD), islet antigen 2 (IA2) and zinc transporter isoform-8 (Znt8) and were defined as having ADM where positive for these antibodies. We then assayed thyroid peroxidase (TPO), tissue transglutaminase (tTG) and 21-hydroxylase (21-OH) autoantibodies in randomly selected participants with ADM and in age-matched, sex-matched and non-ADM controls with T2D plus controls with NGT. RESULTS: Post-normalization, the standardized prevalence rate of ADM was 6.0% (95% confidence interval [CI] 5.3-6.8) in initially non-insulin-requiring participants with ADM, corresponding to six million adults in China, in whom adjusted antibody positivity was: TPO autoantibodies 16.3% (95% CI 10.8-21.8), tTG autoantibodies 2.1% (95% CI 0.0-4.2), and 21-OH autoantibodies 1.8% (95% CI -0.2 to 3.8). Those participants with ADM who were GAD autoantibody-positive had high risk of TPO autoantibody positivity (odds ratio [OR] 2.39, P = 0.0031) and tTG autoantibody positivity (OR 6.98, P = 0.027), while those positive for IA2 autoantibodies had a high risk of tTG autoantibody positivity (OR 19.05, P = 0.001). CONCLUSIONS: A proportion of people with phenotype of T2D in China have ADM, with diabetes-associated autoantibodies, and may be at risk of developing other organ-specific autoimmune diseases; therefore, it may be clinically relevant to consider screening such Chinese populations.

11.
Neural Regen Res ; 13(11): 1995-2004, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30233075

RESUMO

Numerous studies have shown that many patients who suffer from type 2 diabetes mellitus exhibit cognitive dysfunction and neuronal synaptic impairments. Therefore, growing evidence suggests that type 2 diabetes mellitus has a close relationship with occurrence and progression of neurodegeneration and neural impairment in Alzheimer's disease. However, the relationship between metabolic disorders caused by type 2 diabetes mellitus and neurodegeneration and neural impairments in Alzheimer's disease is still not fully determined. Thus, in this study, we replicated a type 2 diabetic animal model by subcutaneous injection of newborn Sprague-Dawley rats with monosodium glutamate during the neonatal period. At 3 months old, the Barnes maze assay was performed to evaluate spatial memory function. Microelectrodes were used to measure electrophysiological function in the hippocampal CA1 region. Western blot assay was used to determine expression levels of glutamate ionotropic receptor NMDA type subunit 2A (GluN2A) and GluN2B in the hippocampus. Enzyme-linked immunosorbent assay was used to determine levels of interleukin-1ß, tumor necrosis factor α, and interleukin-6 in the hippocampus and cerebral cortex, as well as hippocampal amyloid beta (Aß)1-40 and Aß1-42 levels. Our results showed that in the rat model of type 2 diabetes mellitus caused by monosodium glutamate exposure during the neonatal period, latency was prolonged and the number of errors increased in the Barnes maze. Further, latency was increased and time in the escape platform quadrant shortened. Number of times crossing the platform was also reduced in the Morris water maze. After high frequency stimulation of the hippocampus, synaptic transmission was inhibited, expression of GluN2A and GluN2B were decreased in the hippocampus, expression of interleukin 1ß, interleukin 6, and tumor necrosis factor α was increased in the hippocampus and cortex, and levels of Aß1-40 and Aß1-42 were increased in the hippocampus. These findings confirm that type 2 diabetes mellitus induced by neonatal monosodium glutamate exposure results in Alzheimer-like neuropathological changes and further causes cognitive deficits and neurodegeneration in young adulthood.

12.
Neurosci Lett ; 682: 39-44, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-29885453

RESUMO

Epidemiological surveys show that 70-80% of patients with Alzheimer's disease (AD) have type 2 diabetes mellitus (T2DM) or show an abnormality of blood glucose levels. Therefore, an increasing number of evidence has suggested that diabetic hyperglycemia is tightly linked with the pathogenesis and progression of AD. In the present study, we replicated T2DM animal model via subcutaneous injection of newborn Sprague-Dawley (SD) rats with monosodium glutamate (MSG) during the neonatal period to investigate the effects and underlying mechanisms of hyperglycemia on cognitive ability. We found that neonatal MSG exposure induced hyperglycemia as well as Alzheimer-like learning and memory deficits with decreased dendritic spine density and hippocampal synaptic-related protein expression and increased phosphorylated tau levels in ∼3-month-old SD rats. Our results suggested that hyperglycemia probably causes cognitive impairment and Alzheimer-like neuropathological changes, which provide the experimental data connecting T2DM and AD.


Assuntos
Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Aromatizantes/toxicidade , Aprendizagem em Labirinto/efeitos dos fármacos , Glutamato de Sódio/toxicidade , Fatores Etários , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Animais , Animais Recém-Nascidos , Disfunção Cognitiva/psicologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/psicologia , Masculino , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos Sprague-Dawley
13.
J Alzheimers Dis ; 63(4): 1537-1546, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29782322

RESUMO

There is accumulating evidence that decreased histone acetylation is involved in normal aging and neurodegenerative diseases. Recently, we found that ANP32A, a key component of INHAT (inhibitor of acetyltransferases) that suppresses histone acetylation, increased in aged and cognitively impaired C57 mice and expressing wild-type human full length tau (htau) transgenic mice. Downregulating ANP32A restored cognitive function and synaptic plasticity through upregulation of the expressions of synaptic-related proteins via increasing histone acetylation. However, there is no direct evidence that ANP32A can induce neurodegeneration and memory deficits. In the present study, we overexpressed ANP32A in the hippocampal CA3 region of C57 mice and found that ANP32A overexpression induced cognitive abilities and synaptic plasticity deficits, with decreased synaptic-related protein expression and histone acetylation. Combined with our recent studies, our findings reveal that upregulated ANP32A induced-suppressing histone acetylation may underlie the cognitive decline in neurodegenerative disease, and suppression of ANP32A may represent a promising therapeutic approach for neurodegenerative diseases including Alzheimer's disease.


Assuntos
Histonas/metabolismo , Transtornos da Memória/enzimologia , Transtornos da Memória/genética , Proteínas Nucleares/metabolismo , Regulação para Cima/genética , Acetilação , Fatores Etários , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/ultraestrutura , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/patologia , Espinhas Dendríticas/ultraestrutura , Dependovirus/genética , Modelos Animais de Doenças , Potenciais Pós-Sinápticos Excitadores/genética , Potenciais Pós-Sinápticos Excitadores/fisiologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/patologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Nucleares/genética , Receptores de Glutamato/metabolismo , Sinapsinas/metabolismo , Sinaptofisina/metabolismo , Transdução Genética
15.
Exp Ther Med ; 15(1): 173-181, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29250147

RESUMO

Deregulation of microRNA-92b (miR-92b) has been implicated in osteosarcoma. However, the underlying regulatory mechanism of miR-92b in osteosarcoma growth and metastasis remains largely unclear. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were used to measure mRNA and protein expression. MTT and Transwell assays were conducted to determine cell proliferation and invasion, and a luciferase reporter assay was performed to confirm the association between miR-92b and Dickkopf3-related protein (DKK3). The results demonstrated that miR-92b was significantly upregulated in osteosarcoma tissues compared with matched adjacent non-tumor tissues. Additionally, high miR-92b levels were significantly associated with lung metastasis and advanced tumor, node, metastasis stage (P<0.05) but not with age, sex, tumor size, location, serum lactate dehydrogenase or serum alkaline phosphatase. miR-92b expression was also significantly upregulated in osteosarcoma cell lines compared with normal osteoblast cells. Knockdown of miR-92b significantly inhibited the proliferation and invasion of osteosarcoma U2OS cells (P<0.01). By contrast, overexpression of miR-92b significantly increased U2OS cell proliferation and invasion (P<0.01). DKK3 was identified as a target gene of miR-92b and it was demonstrated that DKK3 expression was negatively regulated by miR-92b in U2OS cells. Restoration of DKK3 expression abrogated the increased proliferation and invasion of U2OS cells induced by miR-92b overexpression. Notably, DKK3 was significantly downregulated in osteosarcoma tissues compared with adjacent non-tumor tissues and its expression was inversely correlated to miR-92b levels in osteosarcoma tissues. Taken together, these data indicate that miR-92b promotes cell proliferation and invasion in osteosarcoma by targeting DKK3. Therefore, miR-92b may become a potential therapeutic target for osteosarcoma.

16.
Oncotarget ; 8(50): 87107-87123, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-29152067

RESUMO

Propoxur is considered a prime etiological suspect of increasing tumor incidence, but the role is still undefined. In this study, two human breast cancer cells lines, MCF-7 and MDA-MB-231 cells, were used as cell models. Cells were respectively treated with 0, 0.01, 1, or 100 µM propoxur. PD98059, a MEK inhibitor, was administered to block the ERK/MAPK pathway. Migration and reactive oxygen species were measured by wound healing and Transwell assays, and flow cytometry. Protein expression and subcellular location were detected by western blotting and immunofluorescence staining, respectively. Results showed that propoxur treatment enhanced cell migration and invasion in a dose-dependent manner, while MMP-2 expression, but not MMP-9, was significantly increased in two cell lines. Meanwhile, the treatment increased intracellular reactive oxygen species, Nrf2 expression and nuclear translocation, and ERK1/2 phosphorylation. Inversely, inhibition of ERK1/2 activation with PD98059 significantly attenuated propoxur-induced Nrf2 expression and nuclear translocation. Moreover, PD98059 suppressed propoxur-induced cell migration and invasion, and MMP-2 overexpression. Collectively, these results indicate that propoxur can trigger reactive oxygen species overproduction, further promoting breast cancer cell migration and invasion by regulating the ERK/Nrf2 signaling pathways.

17.
Pediatrics ; 140(6)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29127208

RESUMO

BACKGROUND AND OBJECTIVES: Interventions to prevent childhood obesity targeting school age children have mostly reported limited effectiveness, suggesting such prevention programs may need to start at an earlier age, but evidence has been scarce. We reported a pilot study aiming to demonstrate the feasibility of a multifaceted intervention for preschool children and to provide a preliminary assessment of the effectiveness. METHODS: This nonrandomized controlled trial recruited children aged 3 to 6 years from 6 kindergartens in Guangzhou, China. Based on the preference of the School and Parents Committees, 4 kindergartens (648 children) received a 3-component intervention (training of kindergarten staff, initiating healthy curriculum for children, and close collaboration between families and kindergartens) over 12 months, while the other 2 kindergartens (336 children), serving as controls, received routine health care provision. Outcome measures were the changes in BMI z score between baseline and the end of 12 months, and the prevalence of postintervention children who were overweight or obese. RESULTS: By 12 months, children within the intervention group had a smaller BMI z score increase (0.24) compared to the control (0.41), with a difference of -0.31 (95% CI -0.47 to -0.15). The prevalence of overweight or obesity was also lower among the intervention group at the end of the study (OR: 0.43, 95% CI 0.19 to 0.96), adjusted for baseline status. CONCLUSIONS: Our results indicated a multicomponent health behavior intervention might be effective in reducing the prevalence of obesity, but the longer term effects will need confirmation from randomized controlled trials.


Assuntos
Terapia Comportamental/métodos , Índice de Massa Corporal , Terapia por Exercício/métodos , Obesidade Pediátrica/prevenção & controle , Criança , Pré-Escolar , China/epidemiologia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pais/educação , Obesidade Pediátrica/epidemiologia , Projetos Piloto , Prevalência , Fatores de Tempo , Resultado do Tratamento
18.
Reprod Biomed Online ; 35(5): 555-561, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28784336

RESUMO

The aim of this prospective, randomized, controlled trial was to evaluate the efficacy of different doses of oestrogen treatment (2 mg and 6 mg daily) after hysteroscopic adhesiolysis in patients with moderate to severe adhesion according to the American Fertility Society (AFS) classification of intrauterine adhesions. A total of 121 patients were included in the final analysis. Fifty-nine patients received 2 mg oestrogen daily (low-dose group), and 62 received 6 mg oestrogen daily (high-dose group) for three cycles after surgery. Second- and third-look outpatient hysteroscopy was performed 4 and 8 weeks after the initial surgery. There was no difference in the menstrual pattern and AFS scores before and after surgery between the two groups, and AFS scores at the second- and third-look hysteroscopy were found to be significantly lower than the scores before surgery in both groups (both P < 0.01). While this study did not address the fundamental question of whether oestrogen adjuvant therapy prevents the recurrence of intrauterine adhesions, the findings do not support the use of high-dose oestrogen therapy after hysteroscopic adhesiolysis.


Assuntos
Estrogênios/administração & dosagem , Histeroscopia/métodos , Aderências Teciduais/cirurgia , Doenças Uterinas/cirurgia , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Menstruação , Estudos Prospectivos , Recidiva , Aderências Teciduais/prevenção & controle , Doenças Uterinas/prevenção & controle
19.
Exp Ther Med ; 13(6): 3167-3174, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28587390

RESUMO

MicroRNA (miR) are short non-coding RNA that bind to the 3'-untranslational region of their target genes, inhibiting translation and causing mRNA degradation. miR deregulation has been implicated in human cancer; however, the detailed regulatory mechanism of miR-137 in osteosarcoma (OS) remains largely unknown. In the present study, miR-137 and enhancer of zeste homologue 2 (EZH2) mRNA and protein expression levels were analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. MTT and transwell assays were performed to evaluate cell viability and invasion capacities and a luciferase reporter gene assay was used to determine the targeting relationship. The results of the current study indicated that miR-137 expression was significantly downregulated in OS tissues and cell lines (P<0.01). Moreover, it was observed that low miR-137 expression levels were significantly associated with lung metastasis and advanced TMN stage (P<0.05), but not associated with age, gender, tumor size, location, serum lactate dehydrogenase or serum alkaline phosphatase. Increasing levels of miR-137 significantly inhibited U2OS cell viability and invasion (P<0.01). By contrast, knockdown of miR-137 markedly increased U2OS cell viability and invasion. EZH2 was identified as a direct target gene of miR-137 in U2OS cells by luciferase reporter assay and EZH2 expression was found to be significantly increased in OS tissues and cell lines (P<0.01). EZH2 was significantly downregulated following miR-137 overexpression (P<0.01), and was upregulated following miR-137 knockdown in U2OS cells. Furthermore, EZH2 overexpression significantly attenuated the suppressive effects of miR-137 on U2OS cell viability and invasion (P<0.01), suggesting that miR-137 inhibits the viability and invasion of OS cells by targeting EZH2. Therefore, the results of the current study suggest that the miR-137/EZH2 axis may be a potential target for novel potential therapeutic strategies to treat OS.

20.
J Obstet Gynaecol ; 37(8): 1036-1047, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28657375

RESUMO

This meta-analysis provides an updated and comprehensive estimate of the effects of obesity on metabolic disorders in adolescent polycystic ovary syndrome (PCOS). Relevant articles consistent with the search terms published up to 31 January 2014 were retrieved from PubMed, EMBASE, PsycINFO and CENTRAL. Thirteen articles (16 independent studies) conformed to the inclusion criteria. The evaluated outcomes were the metabolic parameters of obese adolescents with PCOS (case group) relative to normal-weight adolescents with PCOS, or obese adolescents without PCOS. Compared with normal-weight adolescents with PCOS, the case group had significantly lower sex hormone-binding globulin and high-density lipoprotein cholesterol, and significantly higher triglycerides, leptin, fasting insulin, low-density lipoprotein cholesterol and free testosterone levels. Relative to obese adolescents without PCOS, the case group had significantly higher fasting insulin, low-density lipoprotein cholesterol, free testosterone levels and 2-h glucose during the oral glucose tolerance test. These results indicate that metabolic disorders in adolescent PCOS are worsened by concomitant obesity. This study highlights the importance of preventing obesity during the management of adolescent PCOS. Impact statement What is already known about this subject: Obesity and PCOS share many of the same metabolic disorders, for example, hyperandrogenism and hyperinsulinemia with subsequent insulin resistance. Knowledge regarding metabolic features in obese adolescents with PCOS is limited, and there is concern whether obesity and PCOS are related. What do the results of this study add: Relative to PCOS adolescents of normal weight, obese adolescents with PCOS (the case group) had significantly lower SHBG and HDL-C, and significantly higher triglycerides, leptin, fasting insulin, LDL-C and free testosterone levels. The results indicate that metabolic disorders in adolescent PCOS are worsened by concomitant obesity. What are the implications of these findings for clinical practice and/or further research: Obesity, metabolic disorders and PCOS in adolescents are associated. Obesity exacerbates metabolic disorders in adolescent PCOS. This study highlights the importance of preventing obesity during the management of adolescent PCOS. Therapeutic intervention combined with lifestyle modification may provide better treatment for adolescent PCOS. The aetiologies of PCOS combined with obesity in adolescents require further investigation.


Assuntos
Doenças Metabólicas/complicações , Obesidade/complicações , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Adolescente , Glicemia/análise , Índice de Massa Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Leptina/sangue , Doenças Metabólicas/sangue , Doenças Metabólicas/epidemiologia , Obesidade/sangue , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Triglicerídeos/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA