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BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is characterized by progressive myocardial fibro-fatty infiltration accompanied by trabecular disarray. Traditionally, two-dimensional (2D) instead of 3D fractal dimension (FD) analysis has been used to evaluate trabecular disarray. However, the prognostic value of trabecular disorder assessed by 3D FD measurement remains unclear. PURPOSE: To investigate the prognostic value of right ventricular trabecular complexity in ACM patients using 3D FD analysis based on cardiac MR cine images. STUDY TYPE: Retrospective. POPULATION: 85 ACM patients (mean age: 45 ± 17 years, 52 male). FIELD STRENGTH/SEQUENCE: 3.0T/cine imaging, T2-short tau inversion recovery (T2-STIR), and late gadolinium enhancement (LGE). ASSESSMENT: Using cine images, RV (right ventricular) volumetric and functional parameters were obtained. RV trabecular complexity was measured with 3D fractal analysis by box-counting method to calculate 3D-FD. Cox and logistic regression models were established to evaluate the prognostic value of 3D-FD for major adverse cardiac events (MACE). STATISTICAL TESTS: Cox regression and logistic regression to explore the prognostic value of 3D-FD. C-index, time-dependent receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) to evaluate the incremental value of 3D-FD. Intraclass correlation coefficient for interobserver variability. P < 0.05 indicated statistical significance. RESULTS: 26 MACE were recorded during the 60 month follow-up (interquartile range: 48-67 months). RV 3D-FD significantly differed between ACM patients with MACE (2.67, interquartile range: 2.51 ~ 2.81) and without (2.52, interquartile range: 2.40 ~ 2.67) and was a significant independent risk factor for MACE (hazard ratio, 1.02; 95% confidence interval: 1.01, 1.04). In addition, prognostic model fitness was significantly improved after adding 3D-FD to RV global longitudinal strain, LV involvement, and 5-year risk score separately. DATA CONCLUSION: The myocardial trabecular complexity assessed through 3D FD analysis was found associated with MACE and provided incremental prognostic value beyond conventional ACM risk factors. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 1.
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OBJECTIVES: The present study aimed to investigate the incremental prognostic value of the right ventricular fractal dimension (FD), a novel marker of myocardial trabecular complexity by cardiac magnetic resonance (CMR) in patients with arrhythmogenic cardiomyopathy (ACM). METHODS: Consecutive patients with ACM undergoing CMR were followed up for major cardiac events, including sudden cardiac death, aborted cardiac arrest, and appropriate implantable cardioverter defibrillator intervention. Prognosis prediction was compared by Cox regression analysis. We established a multivariable model supplemented with RV FD and evaluated its discrimination by Harrell's C-statistic. We compared the category-free, continuous net reclassification improvement (cNRI) and integrated discrimination index (IDI) before and after the addition of FD. RESULTS: A total of 105 patients were prospectively included from three centers and followed up for a median of 60 (48, 66) months; experienced 36 major cardiac events were recorded. Trabecular FD displayed a strong unadjusted association with major cardiac events (p < 0.05). In the multivariable Cox regression analysis, RV maximal apical FD maintained an independent association with major cardiac events (hazard ratio, 1.31 (1.11-1.55), p < 0.002). The Hosmer-Lemeshow goodness of fit test displayed good fit (X2 = 0.68, p = 0.99). Diagnostic performance was significantly improved after the addition of RV maximal apical FD to the multivariable baseline model, and the continuous net reclassification improvement increased 21% (p = 0.001), and the integrated discrimination index improved 16% (p = 0.045). CONCLUSIONS: In patients with ACM, CMR-assessed myocardial trabecular complexity was independently correlated with adverse cardiovascular events and provided incremental prognostic value. CLINICAL RELEVANCE STATEMENT: The application of FD values for assessing RV myocardial trabeculae may become an accessible and promising parameter in monitoring and early diagnosis of risk factors for adverse cardiovascular events in patients with ACM. KEY POINTS: ⢠Ventricular trabecular morphology, a novel quantitative marker by CMR, has been explored for the first time to determine the severity of ACM. ⢠Patients with higher maximal apical fractal dimension of RV displayed significantly higher cumulative incidence of major cardiac events. ⢠RV maximal apical FD was independently associated with major cardiac events and provided incremental prognostic value in patients with ACM.
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Displasia Arritmogênica Ventricular Direita , Ventrículos do Coração , Humanos , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Displasia Arritmogênica Ventricular Direita/diagnóstico por imagem , Displasia Arritmogênica Ventricular Direita/complicações , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Estudos Prospectivos , Fractais , Adulto , Imageamento por Ressonância Magnética/métodos , Imagem Cinética por Ressonância Magnética/métodos , Morte Súbita CardíacaRESUMO
In spite of the attractive potential application of the dynamic behavior and defect of metal-organic framework (MOF), the achievement of these features is a challenging goal in the MOF research field. Herein, we report a Co(II) MOF, namely, [Co3(L)2(4-PTZ)2(H2O)2]n·solvent (H2L = 5-(isonicotinamido)isophthalic acid, 4-PTZ = 5-(4-pyridyl)-1H-tetrazole), that features dynamic structural transformation behaviors. By varying the coordination configuration of metal center through the removal of coordinated water molecules, the porous compound could undergo structural transformation to give a new crystalline phase with larger pore dimension. Moreover, the new phase features a mesoporous structure originating from the spatial defect that formed with the transformation process, which indicates that the modulation of dynamic behavior of the MOF could be a potential method for the engineering of a spatial defect. In addition, the gas sorption investigation results reveal that the new phase has enhanced selectivity for CO2/N2, CO2/CH4, and C2H2/C2H4 systems compared with that of the pristine phase, suggesting the potential of spatial defect engineering for the tuning of MOF gas sorption properties.
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BACKGROUND: The standard for early traumatic brain injury (TBI) seizure prophylaxis is phenytoin (PHT). Levetiracetam (LEV) has been proposed as an alternative to PHT. The aim of this study was to evaluate the safety and efficacy of LEV on TBI seizure when compared with PHT. METHODS: A search was carried out based on the databases from Pubmed, Embase and the Cochrane database up to May 2015. The relative risk (RR) and the relevant 95% confidence intervals (CI) were determined. RESULTS: Eight observational studies and one randomized controlled trial involving 2035 cases were included. The results indicated that no significant differences in terms of overall seizure (RR = 0.90; 95% CI = 0.51-1.53; p = 0.68), early seizure (RR = 1.06; 95% CI = 0.37-3.07; p = 0.92) and late seizure (RR = 1.10; 95% CI = 0.43-2.79; p = 0.85) occurrence. However, LEV was associated with a lower adverse drug reaction rate (RR = 0.43; 95% CI = 0.23-0.81; p = 0.01). Moreover, there were no significant differences in terms of mortality, length of ICU or hospital stay between groups. CONCLUSIONS: The meta-analysis suggests that LEV appears to have a similar efficacy to PHT on TBI. A better safety profile of LEV is supported by this analysis.
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Anticonvulsivantes/uso terapêutico , Lesões Encefálicas Traumáticas/complicações , Fenitoína/uso terapêutico , Piracetam/análogos & derivados , Convulsões/prevenção & controle , Anticonvulsivantes/efeitos adversos , Humanos , Levetiracetam , Fenitoína/efeitos adversos , Piracetam/efeitos adversos , Piracetam/uso terapêutico , Convulsões/etiologiaRESUMO
BACKGROUND: MicroRNA-133b (miR-133b) has been shown to play a critical role in spinal cord regeneration. The aim of this study was to investigate the cellular role of miR-133b in neural cells. METHODS: PC12 cells and primary cortical neurons (PCNs) were transfected with lenti-miR-133b, lenti-miR-133b inhibitor, plasmid-shRNA-RhoA, plasmid-RhoA and their negative controls. After 48 hours of transfection, the levels of proteins and mRNA or miRNA were evaluated by Western blotting and qRT-PCR, respectively. Moreover, the neurite outgrowth was analyzed by Image J. For pharmacological experiments, inhibitors of MEK1/2 kinase (PD98059), phosphoinositide-3 kinase (PI3K) (LY294002) and ROCK (Y27632) were added into the culture medium. RESULTS: Overexpression of miR-133b in PC12 cells enhanced neurite outgrowth. Conversely, inhibition of miR-133b reduced neurite length. We further identified RhoA as a target and mediator of mir-133b for neurite extension by Western blot and knockdown experiment. Moreover, overexpression of RhoA could attenuate the neurite growth effects of miR-133b. Also, we observed that miR-133b activated MEK/ERK and PI3K/Akt signaling pathway by targeting RhoA. Finally, in PCNs, miR-133b also increased axon growth and attenuated axon growth restrictions from chondroitin sulfate proteoglycans (CSPG). CONCLUSIONS: In summary, our study suggested that miR-133b regulated neurite outgrowth via ERK1/2 and PI3K/Akt signaling pathway by RhoA suppression.
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MicroRNAs/metabolismo , Neuritos/fisiologia , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Células Cultivadas , Córtex Cerebral/citologia , Cromonas/farmacologia , Flavonoides/farmacologia , MicroRNAs/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Morfolinas/farmacologia , Neuritos/efeitos dos fármacos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oligonucleotídeos Antissenso/metabolismo , Células PC12 , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação/efeitos dos fármacos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Quinases Associadas a rho/antagonistas & inibidores , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/antagonistas & inibidores , Proteína rhoA de Ligação ao GTP/genéticaRESUMO
We performed a meta-analysis of the association of transforming growth factor α gene (TGFA) polymorphisms with the risk of cleft lip with or without cleft palate (CL/P) or cleft palate (CP). In total, data from 29 studies were pooled for the following 3 polymorphisms: TGFA/TaqI, TGFA/BamHI, and TGFA/RasI in the TGFA gene. A fixed-effects or random-effects model was used to calculate the pooled odds ratios based on the results from the heterogeneity tests. A significantly increased CL/P or CP risk was observed in persons carrying a C2 allele at the TaqI polymorphism (odds ratio (OR) = 1.70, 95% confidence interval (CI): 1.41, 2.05) compared with those with a C1 allele (OR = 1.57, 95% CI: 1.23, 2.01). For the TGFA/BamHI polymorphism, carriers of the minor A1 allele had an estimated relative decrease in CL/P risk (OR = 0.44, 95% CI: 0.30, 0.64). These associations remained significant when only high-quality studies were included. However, no significant association was observed between the TGFA/RasI variant and CL/P risk. In summary, this meta-analysis provided a robust estimate of the positive association of the TGFA/TaqI polymorphism with both CL/P and CP and suggests that persons with an A1 allele may have a markedly decreased risk of CL/P.
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Fenda Labial/genética , Fissura Palatina/genética , Polimorfismo de Fragmento de Restrição , Fator de Crescimento Transformador alfa/genética , Estudos de Associação Genética , Marcadores Genéticos , Humanos , Modelos Estatísticos , Razão de Chances , Medição de Risco , Fatores de RiscoRESUMO
OBJECTIVES: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty infiltration of atrial and ventricular myocardium resulting in adverse cardiac events. Atrial function has been increasingly recognized as prognostically important for cardiovascular disease. As the right atrial (RA) strain is a sensitive parameter to describe RA function, we aimed to analyze the prognostic value of the RA strain in ARVC. METHODS: RA strain parameters were derived from cardiac magnetic resonance (CMR) images of 105 participants with definite ARVC. The endpoint was defined as a combination of sudden cardiac death, survival cardiac arrest, and appropriate implantable cardioverter-defibrillator intervention. Cox regression and Kaplan-Meier survival analyses were performed to evaluate the association between RA strain parameters and endpoint. Concordance index (C index), net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to assess the incremental value of RA strain in predicting the endpoint. RESULTS: After a median follow-up of 5 years, 36 (34.3%) reaching the endpoint displayed significantly reduced RA strain parameters. At Kaplan-Meier analysis, impaired RA reservoir (RARS) and booster strains (RABS) were associated with an increased risk of the endpoint. After adjusting for conventional risk factors, RARS (hazard ratio [HR], 0.956; p = 0.005) and RABS (HR, 0.906; p = 0.002) resulted as independent predictors for endpoint at Cox regression analyses. In addition, RARS and RABS improved prognostic value to clinical risk factors and CMR morphological and functional predictors (all p < 0.05). CONCLUSION: RARS and RABS were independent predictors for adverse cardiac events, which could provide incremental prognostic value for conventional predictors in ARVC. CRITICAL RELEVANCE STATEMENT: We evaluated the prognostic value of right atrial strain in ARVC patients and suggested cardiologists consider RA strain as a predictive parameter when evaluating the long-term outcome of ARVC patients in order to formulate better clinical therapy. KEY POINTS: ⢠Patients with ARVC had significantly reduced RA strain and strain rates compared with healthy participants. ⢠Participants with lower RA reservoir and booster stains were associated with a significantly higher risk of adverse cardiac events. ⢠RA booster and reservoir strain provide incremental value to conventional parameters.
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We examined the effects of different tillage practices on plough layer soil structure and organic carbon stabilization in black soil farmland with a long-term positioning platform. The wet-sieving method and infrared spectroscopy method were used to investigate the impacts of conventional tillage (CT), no-tillage (NT), sub-soiling tillage (ST), and moldboard plowing tillage (MP) on soil aggregates distribution and organic carbon characteristics in 0-40 cm soil layers. Compared to CT, both NT and ST treatments significantly increased the proportion of large macroaggregates (>2 mm) in the topsoil layer (0-20 cm)and that of small macroaggregates (0.25-2 mm) in the subsoil layer (20-40 cm) for NT, ST, and MP. NT, ST, and MP treatments resulted in higher mean weight dia-meter (MWD) and mean geometric diameter (GMD) of soil aggregates in both the topsoil and subsoil layers. NT treatment improved organic carbon contents in bulk soil and large macroaggregates in the topsoil layer, while ST and MP enhanced organic carbon contents in bulk soil and large macroaggregates in the subsoil layer. The contribution rate of small macroaggregates organic carbon content to the total was between 68.9% and 83.4%. Furthermore, the organic carbon chemical stabilization of soil body and aggregates increased in the topsoil and subsoil layers under NT treatment compared to others. The MWD had a positive correlation with the organic carbon content and chemical stability of soil body and small macroaggregates. These findings offered a theoretical basis for understanding the impacts of different tillage practices on the stability of soil aggregate and organic carbon in black soil region.
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Carbono , Solo , FazendasRESUMO
Clarifying the effect of different maize straw returning methods on soil temperature is crucial for optimizing the management of farmland straw and the efficient utilization of heat resources in the black soil region of Northeast China. To investigate the impacts of straw returning methods on soil temperature, we conducted a field experiment with four treatments during 2018 and 2020, including plough tillage with straw returning (PTSR), rotary tillage with straw returning (RTSR), no-tillage with straw returning (NTSR), and a control treatment of conventional ridge tillage without straw returning (CT). We measured soil temperature and water content at the 5 cm, 15 cm and 30 cm soil layer, and the straw coverage rate during the 3-year maize growth period. We further analyzed the differences of soil temperature in different soil layer under different treatments, accumulated soil temperature and growing degree-days (GDD) above 10 â, daily dynamics of soil temperature, the production efficiency of air accumulated temperature among different treatments, and explored factors causing the difference of soil temperature and the production efficiency of air accumulated temperature. Our results showed that different treatments mainly affected soil temperature from the sowing to emergence stage (S-VE) of maize. The daily average soil temperature showed a trend of CT>PTSR>RTSR>NTSR. The differences of soil temperature under different treatments showed a decreasing trend as growth process advanced and soil depth increased. Compared with the CT treatment, soil temperature at 5 cm depth was decreased by 0.86, 1.84 and 3.50 â for PTSR, RTSR, and NTSR treatments, respectively. NTSR significantly reduced the accumulated temperature of ≥10 â in different soil layers and GDD. The accumulated temperature ≥ 10 â at the 5, 15, and 30 cm soil layers decreased by 216.2, 222.7, and 165.1 â·d, and the GDD decreased by 201.9, 138.7 and 123.9 â·d, respectively. In addition, production efficiency of air accumulated temperature decreased by 9.7% to 15.6% for NTSR. Conclusively, PTSR and RTSR had significant impacts on topsoil temperature during the maize growing period from sowing to emergence, but did not affect the accumulated soil temperature and the production efficiency of air accumulated temperature. However, NTSR significantly reduced topsoil temperature and production efficiency of air accumulated temperature.
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Agricultura , Solo , Agricultura/métodos , Zea mays , Temperatura , Triticum , ChinaRESUMO
By regulating the solvent used for synthesis, two porous Ni-MOFs, namely {[Ni3(BTC)2(TPT)2/3(H2O)4.08(MeOH)0.92]·2DMF·0.5H2O·0.5MeOH}n (1) and {[Ni3(BTC)2(TPT)2(H2O)6]·6DMF}n (2) (H3BTC = 1,3,5-benzenetricarboxylic acid, TPT = 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine, DMF = N,N-dimethylformamide, and MeOH = methanol) were obtained. Compound 1 reveals a rigid 3D framework, while compound 2 shows a flexible 3-fold interpenetrated framework. Compound 1 exhibits a selective adsorption of CO2 due to the sieving effect of the rigid framework containing two types of cages with small apertures. Noteworthily, the flexible compound 2 displays an obviously guest-induced structural transformation. The desolvated compound 2 reveals a much higher capacity toward CO2 and n-C4H10 than those of N2 CH4, C2H6 and C3H8.
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OBJECTIVE: To identify Parkinson's disease (PD)-associated deregulated pathways and genes, to further elucidate the pathogenesis of PD. METHODS: Dataset GSE100054 was downloaded from the Gene Expression Omnibus, and differentially expressed genes (DEGs) in PD samples were identified. Functional enrichment analyses were conducted for the DEGs. The top 10 hub genes in the protein-protein interaction (PPI) network were screened out and used to construct a support vector machine (SVM) model. The expression of the top 10 genes was then validated in another dataset, GSE46129, and a clinical patient cohort. RESULTS: A total of 333 DEGs were identified. The DEGs were clustered into two gene sets that were significantly enriched in 12 pathways, of which 8 were significantly deregulated in PD, including cytokine-cytokine receptor interaction, gap junction, and actin cytoskeleton regulation. The signature of the top 10 hub genes in the PPI network was used to construct the SVM model, which had high performance for predicting PD. Of the 10 genes, GP1BA, GP6, ITGB5, and P2RY12 were independent risk factors of PD. CONCLUSION: Genes such as GP1BA, GP6, P2RY12, and ITGB5 play critical roles in PD pathology through pathways including cytokine-cytokine receptor interaction, gap junctions, and actin cytoskeleton regulation.
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Doença de Parkinson , Perfilação da Expressão Gênica , Humanos , Doença de Parkinson/genética , Mapas de Interação de Proteínas , Fatores de Risco , Máquina de Vetores de SuporteRESUMO
BACKGROUND: The objective of the present study was to observe and analyze the significance of perfusion-weighted imaging for guiding the operation implementation for non-enhanced glioma, and analyze the estimation of the histopathological grade of the non-enhanced glioma and the accuracy of the degree of malignancy degree before surgery. METHODS: Fifty-six patients diagnosed with non-enhanced glioma through conventional magnetic resonance scanning were selected. Before surgery, conventional magnetic resonance scanning and perfusion-weighted imaging were performed on all patients. The property classification was performed with the perfusion-weighted imaging parameters: cerebral blood volume (CBV) and cerebral blood flow (CBF) before surgery. RESULTS: Surgery was performed on the 56 patients. Tumors were excised and processed for histopathological classification and semi-quantitative immunohistochemical analysis of vascular endothelial growth factor (VEGF) levels. Histology was compared after surgery and the classification accuracy rate was analyzed before surgery. Additionally, conventional magnetic resonance scanning and perfusion-weighted imaging were performed on 15 patients during surgery. We compared and analyzed the reference value of perfusion-weighted imaging before and during surgery. Residual diseased tissues were excised; histopathological examination was performed, and semi-quantitative immunohistochemical analysis of VEGF was performed. Regarding maximal magnetic resonance perfusion-weighted imaging measured before surgery, the CBV, CBF, and expression level of VEGF were positively correlated with the pathological grade of tumors. If the CBV and CBF values of the non-enhanced glioma were higher, the grade of malignancy was higher (P<0.01), and the positive expression rate of VEGF was higher (P<0.01). CONCLUSIONS: Magnetic resonance perfusion-weighted imaging can display vessel growth and distribution within non-enhanced gliomas before surgery, and effectively evaluate the histopathological grade and grade of malignancy, and provide accurate guidance for tumor resection during surgery.
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Glioma/diagnóstico por imagem , Glioma/cirurgia , Angiografia por Ressonância Magnética , Monitorização Intraoperatória/métodos , Cirurgia Assistida por Computador , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Adulto JovemRESUMO
Increasing evidence emphasizes the protective role of Eph receptors in synaptic function in the pathological development of Alzheimer's disease (AD); however, their roles in the regulation of hippocampal astrocytes remain largely unknown. Here, we directly investigated the function of astroglial EphB2 on synaptic plasticity in APP/PS1 mice. Using cell isolation and transgene technologies, we first isolated hippocampal astrocytes and evaluated the expression levels of ephrinB ligands and EphB receptors. Then, we stereotaxically injected EphB2-Flox-AAV into the hippocampus of GFAP-cre/APP/PS1 mice and further evaluated hippocampal synaptic plasticity and astroglial function. Interestingly, astrocytic EphB2 expression was significantly increased in APP/PS1 mice in contrast to its expression profile in neurons. Moreover, depressing this astroglial EphB2 upregulation enhanced hippocampal synaptic plasticity, which results from harmful D-serine release. These results provide evidence of the different expression profiles and function of EphB2 between astrocytes and neurons in AD pathology.
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Alzheimer's disease (AD) is the leading cause of dementia and has become an important public health concern. Accumulating evidence indicates that estradiol can both facilitate and impair memory-related processes and, as a result, the precise nature of the role that estradiol plays during AD pathology remains elusive. Therefore, the present study established a mouse model of AD using stereotactic brain injection of Aß1-42 in which the mice were bilaterally ovariectomized to investigate the effects of 17ß-estradiol (E2) treatment during different stages of the AD process (early and late stages). The cognitive deficits associated with this AD model were significantly ameliorated, and there was a significant increase in hippocampal neurogenesis in Aß1-42 mice that received E2 treatment during the early stage of AD pathology. On the other hand, Aß1-42 mice that received E2 treatment during the late stage of AD pathology did not exhibit any improvements in cognitive function or hippocampal neurogenesis. To reveal the mechanisms, underlying these effects, levels of oxidative stress, activity in death-associated pathways, gliosis, and synaptic function were assessed in the hippocampus. The Aß1-42 mice that received E2 treatment during the early stage of AD pathology exhibited significant reductions in the production of nitric oxide (NO) and reactive oxygen species (ROS), a marked decrease in the activation of Cytochrome-c/Bax/Bcl-2/caspase-3 pathway, a notable decrease in the level of gliosis a significant increase in the number of synapses (ultrastructural investigation), and a marked upregulation in synaptic function-related proteins compared to mice that received E2 treatment during the late stage of AD pathology. Taken together, these findings indicate that E2 treatment during the early stage of AD pathology might be an efficient approach to ameliorate the development of this disease.
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Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/toxicidade , Transtornos Cognitivos/tratamento farmacológico , Estradiol/administração & dosagem , Hipocampo/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Fragmentos de Peptídeos/toxicidade , Fatores Etários , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/administração & dosagem , Animais , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/patologia , Esquema de Medicação , Implantes de Medicamento , Feminino , Hipocampo/patologia , Injeções Intraventriculares , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/fisiologia , Fragmentos de Peptídeos/administração & dosagemRESUMO
Astrocytes and apolipoprotein E (apoE) play critical roles in cognitive function, not only under physiological conditions but also in some pathological situations, particularly in the pathological progression of Alzheimer's disease (AD). The regulatory mechanisms underlying the effect of apoE, derived from astrocytes, on cognitive deficits during AD pathology development are unclear. In this study, we generated amyloid precursor protein/apoE knockout (APP/apoEKO) and APP/glial fibrillary acidic protein (GFAP)-apoEKO mice (the AD mice model used in this study was based on the APP-familial Alzheimer disease overexpression) to investigate the role of apoE, derived from astrocytes, in AD pathology and cognitive function. To explore the mechanism, we investigated the amyloidogenic process related transforming growth factor ß/mothers against decapentaplegic homolog 2/signal transducer and activator of transcription 3 (TGF-ß/Smad2/STAT3) signaling pathway and further confirmed by administering TGF-ß-overexpression adeno-associated virus (specific to astrocytes) to APP/GFAP-apoEKO mice and TGF-ß-inhibition adeno-associated virus (specific to astrocytes) to APP/WT mice. Whole body deletion of apoE significantly ameliorated the spatial learning and memory impairment, reduced amyloid ß-protein production and inhibited astrogliosis in APP/apoEKO mice, as well as specific deletion apoE in astrocytes in APP/GFAP-apoEKO mice. Moreover, amyloid ß-protein accumulation was increased due to promotion of amyloidogenesis of APP, and astrogliosis was upregulated by activation of TGF-ß/Smad2/STAT3 signaling. Furthermore, the overexpression of TGF-ß in astrocytes in APP/GFAP-apoEKO mice abrogated the effects of apoE knockout. In contrast, repression of TGF-ß in astrocytes of APP/WT mice exerted a therapeutic effect similar to apoE knockout. These data suggested that apoE derived from astrocytes contributes to the risk of AD through TGF-ß/Smad2/STAT3 signaling activation. These findings enhance our understanding of the role of apoE, derived from astrocytes, in AD and suggest it to be a potential biomarker and therapeutic target for AD.
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Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Apolipoproteínas E/genética , Apolipoproteínas E/fisiologia , Astrócitos/fisiologia , Deleção de Genes , Terapia Genética/métodos , Transtornos da Memória/genética , Memória/fisiologia , Fator de Transcrição STAT3/fisiologia , Transdução de Sinais/genética , Proteína Smad2/fisiologia , Aprendizagem Espacial/fisiologia , Fator de Crescimento Transformador beta/fisiologia , Animais , Modelos Animais de Doenças , Masculino , Camundongos TransgênicosRESUMO
The complete mitochondrial genome of Sinotmethis brachypterus Zheng & Xi, 1985, which was collected from the Gansu Province of China, is reported here. It is 15,662 bp in length and contains 72.6% AT. All Sinotmethis brachypterus protein-coding sequences start with a typical ATN codon, excluding cox1 and nad6. The usual termination codon (TAN) and incomplete stop codons (T, TA) were found from 13 protein-coding genes. All tRNA genes could be folded into the typical cloverleaf secondary structure, excluding trnS(AGN) which forms another structure. The sizes of the large and small ribosomal RNA genes are 1320 and 852 bp, respectively. The AT content of the A + T-rich region is 84.2%.
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Genoma de Inseto/genética , Genoma Mitocondrial/genética , Gafanhotos/genética , Ortópteros/genética , Animais , Composição de Bases/genética , China , Códon de Terminação/genética , DNA Mitocondrial/genética , Fases de Leitura Aberta/genética , RNA Ribossômico/genética , RNA de Transferência/genética , Análise de Sequência de DNA/métodosRESUMO
Exposure to general anesthesia may cause severe neurotoxicity in developing brain due to neuronal apoptosis. Astragaloside IV (AS IV) has antioxidant and antiapoptosis properties; however, its effects on anesthesia-induced neuroapoptosis have not been studied. In the present study, we determined whether AS IV pre-treatment is able to reduce isoflurane exposure-induced neuroapoptosis in rats. New born rats were pre-treated with AS IV or solvent by oral gavage for three days, then exposed to isoflurane. The results showed that pre-treatment of AS IV significantly inhibited isoflurane-induced neural apoptosis in the hippocampus of new born rats, and such protection was accompanied by reduced levels of caspase-3, nuclear factor-κB activation and phosphorylated c-Jun N-terminal kinase, extracellular signal-regulated kinase and increased levels of B-cell lymphoma-2, glycogen synthase kinase-3ß, Klotho and phosphorylated protein kinase B. Furthermore, AS IV pre-treatment significantly alleviated isoflurane-induced oxidative stress and proinflammatory cytokine release in the rat hippocampus and serum. In summery, the results of the study demonstrated that AS IV is able to protect developing brain from anesthesia-induced neuroapoptosis via anti-oxidant and anti-inflammatory activities.
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Biópsia por Agulha Fina , Nódulo da Glândula Tireoide/patologia , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma/cirurgia , Carcinoma Medular/diagnóstico , Carcinoma Medular/patologia , Carcinoma Medular/cirurgia , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Carcinoma Papilar, Variante Folicular/diagnóstico , Carcinoma Papilar, Variante Folicular/patologia , Carcinoma Papilar, Variante Folicular/cirurgia , Diagnóstico Diferencial , Bócio Nodular/diagnóstico , Bócio Nodular/patologia , Bócio Nodular/terapia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/patologia , Doença de Hashimoto/terapia , Humanos , Linfoma/diagnóstico , Linfoma/patologia , Linfoma/cirurgia , Nódulo da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
We reported a case of metanephric adenofibroma in a 10-year-old boy to describe the clinical, radiologic, and pathologic features and discuss its treatment and differential diagnosis. Nephrectomy was performed for the patient; final histopathologic evaluation was that of a metanephric adenofibroma. Epithelial and stromal elements were both positive for WT-1, Vimentin, PAX2, and the epithelial tumor cells were also positive for S100, AE1/AE3, PAX8, CK8/18, EMA and a few cells were positive for CK7. Larger vessel wall components were positive for SMA, Des, caldesmon while capillary components were positive for CD10, CD31, and CD34. CA-9, α-inhibin and CD-56 were negative in the neoplasm. The Ki-67 labeling index was <1%. Metanephric adenofibroma is a rare benign renal tumor; the diagnosis of it relies on pathology and immunohistochemistry. As its rarity, there is no standard treatment for this disease. The majority of patients underwent nephrectomy and had good prognosis, as it is a benign neoplasm.
Assuntos
Adenofibroma/patologia , Neoplasias Renais/patologia , Biomarcadores Tumorais/análise , Criança , Humanos , Imuno-Histoquímica , Masculino , NefrectomiaRESUMO
BACKGROUND: Polymorphisms in immunity-related GTPase family M (IRGM) gene may be associated with inflammatory bowel disease (IBD) by affecting autophagy. However, the genetic association studies on three common variants in IRGM gene (rs13361189, rs4958847 and rs10065172) have shown inconsistent results. METHODOLOGY/ PRINCIPAL FINDINGS: The PubMed and Embase were searched up to June 5, 2013 for studies on the association between three IRGM polymorphisms and IBD risk. Data were extracted and the odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Finally, we performed a meta-analysis of 25 eligible studies in 3 SNPs located at IRGM gene by using a total of 20590 IBD cases and 27670 controls. The analysis showed modest significant association for the rs13361189, rs4958847 and rs10065172 variants in Crohn's disease (CD): the risk estimates for the allele contrast were OR=1.306 (1.200-1.420), p=5.2 × 10(-10), OR=1.182 (1.082-1.290), p=0.0002, and OR=1.248 (1.057-1.473), p=0.009 respectively (still significant when the p value was Bonferroni adjusted to 0.017). When stratified by ethnicity, significantly increased CD risk was observed in Europeans, but not in Asians. Conversely, there was no association of rs13361189 or rs4958847 variant with risk of ulcerative colitis (UC). CONCLUSIONS/ SIGNIFICANCE: These results indicated that autophagy gene-IRGM polymorphisms appear to confer susceptibility to CD but not UC, especially in Europeans. Our data may provide further understanding of the role of autophagy in the pathogenesis of CD.