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1.
Environ Toxicol ; 39(7): 3930-3943, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38572829

RESUMO

The number of patients with chronic kidney disease (CKD) is increasing. Oral toxin adsorbents may provide some value. Several uremic toxins, including indoxyl sulfate (IS), p-cresol (PCS), acrolein, per- and poly-fluoroalkyl substances (PFAS), and inflammation markers (interleukin 6 [IL-6] and tumor necrosis factor [TNF]-alpha) have been shown to be related to CKD progression. A total of 81 patients taking oral activated charcoal toxin adsorbents (AC-134), which were embedded in capsules that dissolved in the terminal ileum, three times a day for 1 month, were recruited. The renal function, hemoglobulin (Hb), inflammation markers, three PFAS (PFOA, PFOS, and PFNA), and acrolein were quantified. Compared with the baseline, an improved glomerular filtration rate (GFR) and significantly lower acrolein were noted. Furthermore, the CKD stage 4 and 5 group had significantly higher concentrations of IS, PCS, IL-6, and TNF but lower levels of Hb and PFAS compared with the CKD Stage 3 group at baseline and after the intervention. Hb was increased only in the CKD Stage 3 group after the trial (p = .032). Acrolein did not differ between the different CKD stage groups. Patients with improved GFR (responders) (about 77%) and nonresponders had similar baseline GFR. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, indicating a better digestion function. Both the higher PFOA and lower acrolein may be related to improved eGFR (and possibly to improvements in proteinuria, which we did not measure. Proteinuria is associated with PFAS loss in the urine), AC-134 showed the potential to improve the GFR and decrease acrolein, which might better indicate renal function change. Future studies are needed with longer follow-ups.


Assuntos
Taxa de Filtração Glomerular , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Insuficiência Renal Crônica/fisiopatologia , Idoso , Pessoa de Meia-Idade , Taxa de Filtração Glomerular/efeitos dos fármacos , Cresóis , Acroleína , Adsorção , Toxinas Urêmicas , Concentração de Íons de Hidrogênio , Indicã/urina , Carvão Vegetal/química , Carvão Vegetal/administração & dosagem , Rim/efeitos dos fármacos , Rim/fisiopatologia , Cápsulas , Administração Oral
2.
J Comput Assist Tomogr ; 47(5): 811-819, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37707413

RESUMO

OBJECTIVE: To compare the image quality of short-tau inversion recovery (STIR) and the STIR-slice encoding for metal artifact correction (SEMAC) sequence for postsurgery spine magnetic resonance imaging (MRI). METHODS: Twenty-nine patients with metallic spinal implants who underwent spinal 1.5 T MRI with STIR and STIR-SEMAC sequences between July 2016 and November 2020 were retrospectively enrolled. Qualitative assessments were performed using 5-point scales; higher scores indicated better image quality. For screw metal artifact analysis, scores were obtained for artifacts on vertebral bodies and neural foramina, screw artifact widths, and bone marrow signal intensities. For patient-based analysis, scores were obtained for imaging quality and fat suppression quality, signal intensity, and cerebrospinal fluid noise. A paired t test was performed for statistical analyses. RESULTS: We analyzed 163 screws in 29 patients. In the screw metal artifact analysis, the vertebral body and neural foramen scores were significantly higher for the STIR-SEMAC images than for the STIR (all P < 0.001). The artifact width in the STIR-SEMAC images (9.8 ± 3.4 mm) was significantly smaller than that in the STIR images (16.0 ± 4.7 mm, P < 0.001). In patient-based analysis, the fat suppression and imaging quality scores were significantly higher for the STIR-SEMAC images than for the STIR images (all P < 0.001). The cerebrospinal fluid signal intensity, noise, and signal-to-noise ratios were significantly higher for the STIR images (all P < 0.005). CONCLUSIONS: Short-tau inversion recovery-SEMAC sequences provide good metallic artifact reduction and fat suppression for postsurgery spine 1.5 T MRI.


Assuntos
Artefatos , Metais , Humanos , Estudos Retrospectivos , Próteses e Implantes , Imageamento por Ressonância Magnética/métodos , Aumento da Imagem/métodos
3.
Sensors (Basel) ; 22(4)2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-35214561

RESUMO

In this paper, an effective electrocardiogram (ECG) recurrence plot (RP)-based arrhythmia classification algorithm that can be implemented in portable devices is presented. Public databases from PhysioNet were used to conduct this study including the MIT-BIH Atrial Fibrillation Database, the MIT-BIH Arrhythmia Database, the MIT-BIH Malignant Ventricular Ectopy Database, and the Creighton University Ventricular Tachyarrhythmia Database. ECG time series were segmented and converted using an RP, and two-dimensional images were used as inputs to the CNN classifiers. In this study, two-stage classification is proposed to improve the accuracy. The ResNet-18 architecture was applied to detect ventricular fibrillation (VF) and noise during the first stage, whereas normal, atrial fibrillation, premature atrial contraction, and premature ventricular contractions were detected using ResNet-50 in the second stage. The method was evaluated using 5-fold cross-validation which improved the results when compared to previous studies, achieving first and second stage average accuracies of 97.21% and 98.36%, sensitivities of 96.49% and 97.92%, positive predictive values of 95.54% and 98.20%, and F1-scores of 95.96% and 98.05%, respectively. Furthermore, a 5-fold improvement in the memory requirement was achieved when compared with a previous study, making this classifier feasible for use in resource-constricted environments such as portable devices. Even though the method is successful, first stage training requires combining four different arrhythmia types into one label (other), which generates more data for the other category than for VF and noise, thus creating a data imbalance that affects the first stage performance.


Assuntos
Taquicardia Ventricular , Complexos Ventriculares Prematuros , Algoritmos , Eletrocardiografia/métodos , Humanos , Processamento de Sinais Assistido por Computador , Taquicardia Ventricular/diagnóstico , Fibrilação Ventricular/diagnóstico , Complexos Ventriculares Prematuros/diagnóstico
4.
Int J Mol Sci ; 23(19)2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36232980

RESUMO

Oxygen glucose deprivation (OGD) can produce hypoxia-induced neurotoxicity and is a mature in vitro model of hypoxic cell damage. Activated AMP-activated protein kinase (AMPK) regulates a downstream pathway that substantially increases bioenergy production, which may be a key player in physiological energy and has also been shown to play a role in regulating neuroprotective processes. Resveratrol is an effective activator of AMPK, indicating that it may have therapeutic potential as a neuroprotective agent. However, the mechanism by which resveratrol achieves these beneficial effects in SH-SY5Y cells exposed to OGD-induced inflammation and oxidative stress in a 3D gelatin scaffold remains unclear. Therefore, in the present study, we investigated the effect of resveratrol in 3D gelatin scaffold cells to understand its neuroprotective effects on NF-κB signaling, NLRP3 inflammasome, and oxidative stress under OGD conditions. Here, we show that resveratrol improves the expression levels of cell viability, inflammatory cytokines (TNF-α, IL-1ß, and IL-18), NF-κB signaling, and NLRP3 inflammasome, that OGD increases. In addition, resveratrol rescued oxidative stress, nuclear factor-erythroid 2 related factor 2 (Nrf2), and Nrf2 downstream antioxidant target genes (e.g., SOD, Gpx GSH, catalase, and HO-1). Treatment with resveratrol can significantly normalize OGD-induced changes in SH-SY5Y cell inflammation, oxidative stress, and oxidative defense gene expression; however, these resveratrol protective effects are affected by AMPK antagonists (Compounds C) blocking. These findings improve our understanding of the mechanism of the AMPK-dependent protective effect of resveratrol under 3D OGD-induced inflammation and oxidative stress-mediated cerebral ischemic stroke conditions.


Assuntos
Neuroblastoma , Fármacos Neuroprotetores , Proteínas Quinases Ativadas por AMP/metabolismo , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Catalase/metabolismo , Gelatina/farmacologia , Glucose/metabolismo , Humanos , Inflamassomos/metabolismo , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Interleucina-18/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neuroblastoma/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Oxigênio/metabolismo , Resveratrol/metabolismo , Resveratrol/farmacologia , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
5.
Sensors (Basel) ; 21(18)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34577471

RESUMO

This study evaluates cardiovascular and cerebral hemodynamics systems by only using non-invasive electrocardiography (ECG) signals. The Massachusetts General Hospital/Marquette Foundation (MGH/MF) and Cerebral Hemodynamic Autoregulatory Information System Database (CHARIS DB) from the PhysioNet database are used for cardiovascular and cerebral hemodynamics, respectively. For cardiovascular hemodynamics, the ECG is used for generating the arterial blood pressure (ABP), central venous pressure (CVP), and pulmonary arterial pressure (PAP). Meanwhile, for cerebral hemodynamics, the ECG is utilized for the intracranial pressure (ICP) generator. A deep convolutional autoencoder system is applied for this study. The cross-validation method with Pearson's linear correlation (R), root mean squared error (RMSE), and mean absolute error (MAE) are measured for the evaluations. Initially, the ECG is used to generate the cardiovascular waveform. For the ABP system-the systolic blood pressure (SBP) and diastolic blood pressures (DBP)-the R evaluations are 0.894 ± 0.004 and 0.881 ± 0.005, respectively. The MAE evaluations for SBP and DBP are, respectively, 6.645 ± 0.353 mmHg and 3.210 ± 0.104 mmHg. Furthermore, for the PAP system-the systolic and diastolic pressures-the R evaluations are 0.864 ± 0.003 mmHg and 0.817 ± 0.006 mmHg, respectively. The MAE evaluations for systolic and diastolic pressures are, respectively, 3.847 ± 0.136 mmHg and 2.964 ± 0.181 mmHg. Meanwhile, the mean CVP evaluations are 0.916 ± 0.001, 2.220 ± 0.039 mmHg, and 1.329 ± 0.036 mmHg, respectively, for R, RMSE, and MAE. For the mean ICP evaluation in cerebral hemodynamics, the R and MAE evaluations are 0.914 ± 0.003 and 2.404 ± 0.043 mmHg, respectively. This study, as a proof of concept, concludes that the non-invasive cardiovascular and cerebral hemodynamics systems can be potentially investigated by only using the ECG signal.


Assuntos
Determinação da Pressão Arterial , Eletrocardiografia , Pressão Sanguínea , Hemodinâmica , Redes Neurais de Computação
6.
Int J Mol Sci ; 22(23)2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34884542

RESUMO

Particulate matter exposure has been known as a potential risk for the global burden of disease, such as respiratory and cardiovascular diseases. Accumulating evidence suggests that PM2.5 (particulate matter with a diameter less than 2.5 µm) is associated with increased risk of kidney disease, but the mechanisms underlying the renal injury caused by PM2.5 remain to be elucidated. This study investigated the effects of PM2.5 on human proximal tubular epithelial (HK-2) cells by monolayer and 3D spheroid cultures and explored the potential mechanisms. The typical morphology of HK-2 cells showed epithelial-mesenchymal transition (EMT), resulting in reduced adhesion and enhanced migration after PM2.5 exposure, and was accompanied by decreased E-cadherin expression and increased vimentin and α-SMA expressions. Exposure to PM2.5 in the HK-2 cells could lead to an increase in interleukin-6 (IL-6) levels and cause the activation of signal transducer and activator of transcription 3 (STAT3), which is involved in EMT features of HK-2 cells. Furthermore, blocking IL-6/STAT3 signaling by an IL-6 neutralizing antibody or STAT3 inhibitor was sufficient to reverse PM2.5-induced EMT characteristics of the HK-2 cells. Our study suggests that PM2.5 could induce early renal tubule cell injury, contributing to EMT change, and the induction of IL-6/STAT3 pathway may play an important role in this process.


Assuntos
Células Epiteliais/patologia , Transição Epitelial-Mesenquimal , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-6/metabolismo , Túbulos Renais Proximais/patologia , Material Particulado/efeitos adversos , Fator de Transcrição STAT3/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Interleucina-6/genética , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Fator de Transcrição STAT3/genética
7.
Sensors (Basel) ; 20(14)2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32660088

RESUMO

Hypertension affects a huge number of people around the world. It also has a great contribution to cardiovascular- and renal-related diseases. This study investigates the ability of a deep convolutional autoencoder (DCAE) to generate continuous arterial blood pressure (ABP) by only utilizing photoplethysmography (PPG). A total of 18 patients are utilized. LeNet-5- and U-Net-based DCAEs, respectively abbreviated LDCAE and UDCAE, are compared to the MP60 IntelliVue Patient Monitor, as the gold standard. Moreover, in order to investigate the data generalization, the cross-validation (CV) method is conducted. The results show that the UDCAE provides superior results in producing the systolic blood pressure (SBP) estimation. Meanwhile, the LDCAE gives a slightly better result for the diastolic blood pressure (DBP) prediction. Finally, the genetic algorithm-based optimization deep convolutional autoencoder (GDCAE) is further administered to optimize the ensemble of the CV models. The results reveal that the GDCAE is superior to either the LDCAE or UDCAE. In conclusion, this study exhibits that systolic blood pressure (SBP) and diastolic blood pressure (DBP) can also be accurately achieved by only utilizing a single PPG signal.


Assuntos
Pressão Arterial , Determinação da Pressão Arterial , Hipertensão , Fotopletismografia , Pressão Sanguínea , Humanos , Hipertensão/diagnóstico
9.
Exp Cell Res ; 370(2): 312-321, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29964054

RESUMO

Peroxisome proliferator-activated receptor gamma (PPARγ) belongs to a family of ligand-activated nuclear receptors known to regulate many crucial physiological and pathological conditions. Indeed, altered PPARγ transcriptional activity contributes to metabolic syndromes (obesity and hyperglycemia associated with type 2 diabetes mellitus), stroke and neurodegenerative diseases. Various studies suggest that PPARγ agonists influence neuronal deficits in Alzheimer's Disease (AD) patients and rodent models of AD. Expression of amyloid-beta (Aß), a neuropathological marker associated with the pathogenesis of AD neuronal impairment, is inversely correlated with the activation of PPARγ-dependent neuroprotective responses. Nevertheless, molecular mechanisms by which the effects of PPARγ agonists in AD remain to be clarified. Here, we explore the PPARγ signaling pathways and networks that protect against Aß-induced endoplasmic reticulum (ER) stress (e.g., caspase 4, Bip, CHOP, ASK1 and ER calcium), cell death (e.g., viability and cytochrome c) and mitochondrial deficiency (e.g., maximal respiratory function, COX activity, and mitochondrial membrane potential) events in the human neural stem cells (hNSCs) treated with Aß. Co-treatment with GW9662 (an antagonist of PPARγ) effectively blocked these protective effects by rosiglitazone, providing strong evidence that PPARγ-dependent signaling rescues hNSCs from Aß-mediated toxicity. Together, our data suggest activation of PPARγ pathway might be critical to protecting against AD-related ER stress, ER disequilibrium and mitochondrial deficiency. These findings also improve our understanding of the role of PPARγ in hNSCs, and may aid in the development and implementation of new therapeutic strategies for the treatment of AD.


Assuntos
Peptídeos beta-Amiloides/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , PPAR gama/efeitos dos fármacos , Rosiglitazona/farmacologia , Peptídeos beta-Amiloides/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Células-Tronco Neurais/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , PPAR gama/metabolismo
10.
Skeletal Radiol ; 48(10): 1637-1641, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30868231

RESUMO

Intraosseous myoepithelial carcinoma is an extremely rare type of bone tumor that most often presents in the long tubular bones, but also occurs in small tubular bones and the axial skeleton. We report the radiographic images and complete magnetic resonance (MR) features of a 44-year-old male with right knee pain of 7 months' duration. The radiographic findings and convention MR images indicated a giant cell tumor of the bone. The dynamic contrast-enhanced images showed a patent with the early wash-in and early wash-out usually noted in a giant cell tumor of the bone. Only water restriction on diffusion-weighted imaging (DWI) showed the malignant impression. Care should be taken when conventional images indicate giant cell tumor of the bone, as intraosseous myoepithelial carcinoma, although rare, can mimic this more common diagnosis. Further studies with DWI are warranted.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Tumores de Células Gigantes , Imageamento por Ressonância Magnética/métodos , Mioepitelioma/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Humanos , Masculino
11.
Skeletal Radiol ; 48(7): 1145-1148, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30729263

RESUMO

Fracture of the polyethylene tibial post in the posterior-stabilized total knee prosthesis is often delayed in diagnosis due to its nonspecific symptoms and the radiolucent characteristic of polyethylene on conventional radiography. Therefore, the diagnosis is always established by arthroscopy. Notwithstanding recent advances in imaging modalities, we are presently aware of only two related case reports on MRI and even no reports about arthrographic or CT-arthrographic diagnosis of fractured tibial post. We hereby report a case of a 58-year-old female patient who developed recurrent knee pain during the third year after total knee arthroplasty. The displaced polyethylene tibial post was clearly outlined by administered contrast material in the posterior knee. Under the diagnosis of fracture of the tibial post, the patient underwent isolated replacement of the broken polyethylene insert. Her knee pain significantly improved after the operation.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Falha de Prótese , Tomografia Computadorizada por Raios X , Artroscopia , Meios de Contraste , Feminino , Humanos , Pessoa de Meia-Idade , Polietileno , Desenho de Prótese , Reoperação
12.
Sensors (Basel) ; 19(7)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30965619

RESUMO

Within Internet of Things (IoT) sensors, the challenge is how to dig out the potentially valuable information from the collected data to support decision making. This paper proposes a method based on machine learning to predict long cycle maintenance time of wind turbines for efficient management in the power company. Long cycle maintenance time prediction makes the power company operate wind turbines as cost-effectively as possible to maximize the profit. Sensor data including operation data, maintenance time data, and event codes are collected from 31 wind turbines in two wind farms. Data aggregation is performed to filter out some errors and get significant information from the data. Then, the hybrid network is built to train the predictive model based on the convolutional neural network (CNN) and support vector machine (SVM). The experimental results show that the prediction of the proposed method reaches high accuracy, which helps drive up the efficiency of wind turbine maintenance.

13.
Pediatr Allergy Immunol ; 29(7): 732-739, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30054929

RESUMO

BACKGROUND: Urticaria is one of the most common diseases seen in clinical practice, whereas several reports have proposed that urticaria may have a link with autoimmune disorders. Few studies have examined the clinical association between urticaria with systemic lupus erythematosus (SLE). By conducting a nationwide population-based case-control study in Taiwan, we evaluated the risk of SLE in children with a prior clinical diagnosis of urticaria. METHODS: Using 2000-2011 claims data from the Taiwanese National Health Insurance Research Database, we identified 2105 SLE children during 2004-2011 as the study group, along with randomly selected 8420 non-SLE patients matched (1:4) for age, sex, and first diagnosis date as the control group. The correlation between urticaria and SLE risk was estimated using conditional logistic regression analysis. RESULTS: The prevalence rates of clinically diagnosed acute and chronic urticaria in SLE patients were 22.09% and 18.24%, respectively. A significant association was found between clinically diagnosed urticaria and childhood SLE, with a stronger risk associated with more episodes of urticaria (≥3 visits, OR: 2.33, 95% CI 1.91-2.84). The risk was higher with chronic urticaria (OR: 2.21, 95% CI 1.85-2.64) than with acute urticaria (OR: 1.54, 95% CI 1.34-1.76). Subgroup analysis stratified by sex or age indicated that the risk associated with SLE was significantly greater among female children and adolescents with urticaria. CONCLUSIONS: Our results suggest that children with urticaria have a significantly higher risk of SLE, with the risk increasing further among those with more episodes of urticaria or chronic urticaria.


Assuntos
Lúpus Eritematoso Sistêmico/epidemiologia , Urticária/complicações , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/etiologia , Masculino , Prevalência , Fatores de Risco , Taiwan/epidemiologia
14.
Exp Cell Res ; 359(2): 367-373, 2017 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-28821394

RESUMO

Advanced glycosylation end products (AGEs) formation is correlated with the pathogenesis of diabetic neuronal damage, but its links with oxidative stress are still not well understood. Metformin, one of the most widely used anti-diabetic drugs, exerts its effects in part by activation of AMP-activated protein kinase (AMPK). Once activated, AMPK regulates many pathways central to metabolism and energy balance including, glucose uptake, glycolysis and fatty acid oxidation. AMPK is also present in neurons, but its role remains unclear. Here, we show that AGE exposure decreases cell viability of human neural stem cells (hNSCs), and that the AMPK agonist metformin reverses this effect, via AMPK-dependent downregulation of RAGE levels. Importantly, hNSCs co-treated with metformin were significantly rescued from AGE-induced oxidative stress, as reflected by the normalization in levels of reactive oxygen species. In addition, compared to AGE-treated hNSCs, metformin co-treatment significantly reversed the activity and mRNA transcript level changes of SOD1/2 and Gpx. Furthermore, hNSCs exposed to AGEs had significantly lower mRNA levels among other components of normal cellular oxidative defenses (GSH, Catalase and HO-1), which were all rescued by co-treatment with metformin. This metformin-mediated protective effect on hNSCs for of both oxidative stress and oxidative defense genes by co-treatment with metformin was blocked by the addition of an AMPK antagonist (Compound C). These findings unveil the protective role of AMPK-dependent metformin signaling during AGE mediated oxidative stress in hNSCs, and suggests patients undergoing AGE-mediated neurodegeneration may benefit from the novel therapeutic use of metformin.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Produtos Finais de Glicação Avançada/farmacologia , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Células-Tronco Neurais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Catalase/genética , Catalase/metabolismo , Proliferação de Células , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica , Glutationa/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo
15.
Exp Cell Res ; 352(1): 75-83, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28159472

RESUMO

A growing body of evidence suggests type 2 diabetes mellitus (T2DM) is linked to neurodegenerative diseases such as Alzheimer's disease (AD). Although the precise mechanisms remain unclear, T2DM may exacerbate neurodegenerative processes. AMP-activated protein kinase (AMPK) signaling is an evolutionary preserved pathway that is important during homeostatic energy biogenesis responses at both the cellular and whole-body levels. Metformin, a ubiquitously prescribed anti-diabetic drug, exerts its effects by AMPK activation. However, while the roles of AMPK as a metabolic mediator are generally well understood, its performance in neuroprotection and neurodegeneration are not yet well defined. Given hyperglycemia is accompanied by an accelerated rate of advanced glycosylation end product (AGE) formation, which is associated with the pathogenesis of diabetic neuronal impairment and, inflammatory response, clarification of the role of AMPK signaling in these processes is needed. Therefore, we tested the hypothesis that metformin, an AMPK activator, protects against diabetic AGE induced neuronal impairment in human neural stem cells (hNSCs). In the present study, hNSCs exposed to AGE had significantly reduced cell viability, which correlated with elevated inflammatory cytokine expression, such as IL-1α, IL-1ß, IL-2, IL-6, IL-12 and TNF-α. Co-treatment with metformin significantly abrogated the AGE-mediated effects in hNSCs. In addition, metformin rescued the transcript and protein expression levels of acetyl-CoA carboxylase (ACC) and inhibitory kappa B kinase (IKK) in AGE-treated hNSCs. NF-κB is a transcription factor with a key role in the expression of a variety of genes involved in inflammatory responses, and metformin did prevent the AGE-mediated increase in NF-κB mRNA and protein levels in the hNSCs exposed to AGE. Indeed, co-treatment with metformin significantly restored inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels in AGE-treated hNSCs. These findings extend our understanding of the central role of AMPK in AGE induced inflammatory responses, which increase the risk of neurodegeneration in diabetic patients.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Produtos Finais de Glicação Avançada/efeitos adversos , Hipoglicemiantes/farmacologia , Inflamação/prevenção & controle , Metformina/farmacologia , Células-Tronco Neurais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/genética , Apoptose/efeitos dos fármacos , Western Blotting , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais
16.
Phys Rev Lett ; 118(16): 166802, 2017 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-28474942

RESUMO

Supersymmetric (SUSY) gauge theories such as the minimal supersymmetric standard model play a fundamental role in modern particle physics, but have not been verified so far in nature. Here, we show that a SUSY gauge theory with dynamical gauge bosons and fermionic gauginos emerges naturally at the pair-density-wave (PDW) quantum phase transition on the surface of a correlated topological insulator hosting three Dirac cones, such as the topological Kondo insulator SmB_{6}. At the quantum tricritical point between the surface Dirac semimetal and nematic PDW phases, three massless bosonic Cooper pair fields emerge as the superpartners of three massless surface Dirac fermions. The resulting low-energy effective theory is the supersymmetric XYZ model, which is dual by mirror symmetry to N=2 supersymmetric quantum electrodynamics in 2+1 dimensions, providing a first example of emergent supersymmetric gauge theory in condensed matter systems. Supersymmetry allows us to determine certain critical exponents and the optical conductivity of the surface states at the strongly coupled tricritical point exactly, which may be measured in future experiments.

17.
Nephrol Dial Transplant ; 32(10): 1683-1690, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28011646

RESUMO

BACKGROUND: Infections are a major cause of morbidity in patients with systemic lupus erythematosus (SLE), and may lead to death. No nationally representative study of patients with SLE has examined the rates of infection-related hospitalization and the risk of end-stage renal disease (ESRD). METHODS: We conducted a nationwide cohort study of 7326 patients with newly diagnosed SLE and no history of ESRD. All data were from Taiwan's National Health Insurance claims database for the period 2000-11. RESULTS: Among all SLE patients, 316 (4.3%) developed ESRD (mean follow-up time: 8.1 years). Multivariate Cox regression analysis indicated that the risk of ESRD increased with the number of infection-related hospitalizations. For patients with three or more infection-related admissions, the hazard ratio (HR) for ESRD was 5.08 [95% confidence interval (CI): 3.74-6.90] relative to those with no infection-related admission. Analysis by type of infection indicated that bacteremia patients had the greatest risk for ESRD (HR: 4.82; 95% CI: 3.40-6.85). Analysis of age of SLE onset indicated that patients with juvenile-onset (<18 years) and three or more infection-related hospitalizations had a greatly increased risk for ESRD (HR: 14.49; 95% CI: 5.34-39.33). CONCLUSIONS: Infection-related hospitalizations are associated with a significantly increased risk of ESRD in patients with SLE, especially those with juvenile-onset SLE. Among patients with different types of infectious diseases, those with bacteremia were more likely to develop ESRD.


Assuntos
Infecções Bacterianas/etiologia , Falência Renal Crônica/etiologia , Lúpus Eritematoso Sistêmico/complicações , Adolescente , Adulto , Idade de Início , Infecções Bacterianas/mortalidade , Infecções Bacterianas/terapia , Estudos de Coortes , Feminino , Hospitalização , Humanos , Incidência , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Lúpus Eritematoso Sistêmico/mortalidade , Lúpus Eritematoso Sistêmico/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de Risco , Adulto Jovem
18.
Sensors (Basel) ; 17(11)2017 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-29068369

RESUMO

This study evaluates four databases from PhysioNet: The American Heart Association database (AHADB), Creighton University Ventricular Tachyarrhythmia database (CUDB), MIT-BIH Arrhythmia database (MITDB), and MIT-BIH Noise Stress Test database (NSTDB). The ANSI/AAMI EC57:2012 is used for the evaluation of the algorithms for the supraventricular ectopic beat (SVEB), ventricular ectopic beat (VEB), atrial fibrillation (AF), and ventricular fibrillation (VF) via the evaluation of the sensitivity, positive predictivity and false positive rate. Sample entropy, fast Fourier transform (FFT), and multilayer perceptron neural network with backpropagation training algorithm are selected for the integrated detection algorithms. For this study, the result for SVEB has some improvements compared to a previous study that also utilized ANSI/AAMI EC57. In further, VEB sensitivity and positive predictivity gross evaluations have greater than 80%, except for the positive predictivity of the NSTDB database. For AF gross evaluation of MITDB database, the results show very good classification, excluding the episode sensitivity. In advanced, for VF gross evaluation, the episode sensitivity and positive predictivity for the AHADB, MITDB, and CUDB, have greater than 80%, except for MITDB episode positive predictivity, which is 75%. The achieved results show that the proposed integrated SVEB, VEB, AF, and VF detection algorithm has an accurate classification according to ANSI/AAMI EC57:2012. In conclusion, the proposed integrated detection algorithm can achieve good accuracy in comparison with other previous studies. Furthermore, more advanced algorithms and hardware devices should be performed in future for arrhythmia detection and evaluation.


Assuntos
Arritmias Cardíacas/diagnóstico , Eletrocardiografia/instrumentação , Dispositivos Eletrônicos Vestíveis/normas , Algoritmos , Humanos , Redes Neurais de Computação , Processamento de Sinais Assistido por Computador
19.
Int J Mol Sci ; 18(12)2017 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-29258283

RESUMO

Astragalus membranaceus is commonly used in traditional Chinese medicine for strengthening the host defense system. Astragalus membranaceus-polysaccharides is an effective component with various important bioactivities, such as immunomodulation, antioxidant, anti-diabetes, anti-inflammation and neuroprotection. In the present study, we determine the effects of Astragalus membranaceus-polysaccharides on metabolically stressed transgenic mice in order to develop this macromolecules for treatment of sporadic Alzheimer's disease, a neurodegenerative disease with metabolic risk factors. Transgenic mice, at 10 weeks old prior to the appearance of senile plaques, were treated in combination of administrating high-fat diet and injecting low-dose streptozotocin to create the metabolically stressed mice model. Astragalus membranaceus-polysaccharides was administrated starting at 14 weeks for 7 weeks. We found that Astragalus membranaceus-polysaccharides reduced metabolic stress-induced increase of body weight, insulin and insulin and leptin level, insulin resistance, and hepatic triglyceride. Astragalus membranaceus-polysaccharides also ameliorated metabolic stress-exacerbated oral glucose intolerance, although the fasting blood glucose was only temporally reduced. In brain, metabolic stress-elicited astrogliosis and microglia activation in the vicinity of plaques was also diminished by Astragalus membranaceus-polysaccharides administration. The plaque deposition, however, was not significantly affected by Astragalus membranaceus-polysaccharides administration. These findings suggest that Astragalus membranaceus-polysaccharides may be used to ameliorate metabolic stress-induced diabesity and the subsequent neuroinflammation, which improved the behavior performance in metabolically stressed transgenic mice.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Astragalus propinquus/química , Disfunção Cognitiva/tratamento farmacológico , Fígado Gorduroso/tratamento farmacológico , Obesidade/tratamento farmacológico , Polissacarídeos/uso terapêutico , Doença de Alzheimer/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Fígado Gorduroso/metabolismo , Feminino , Masculino , Camundongos , Obesidade/metabolismo
20.
Skeletal Radiol ; 45(7): 991-6, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27003387

RESUMO

This case subject is a 1-year-old girl presenting with recurrent diffuse soft-tissue swelling of the scalp and periorbital region. Her family denied any known history of trauma. There was no obvious discoloration or local heat at the lesion. Magnetic resonance imaging (MRI) revealed diffuse soft tissue swelling of the scalp manifesting as high signal intensity on T2-weighted images and low signal intensity on T1-weighted images with diffuse enhancement after gadolinium-contrast administration. Biopsy yielded inconclusive pathological results. Fibrodysplasia ossificans progressiva (FOP) was not suspected until malformation of the patient's toes was noticed. The scalp lesion underwent spontaneous regression, and subsequent radiographs of the chest and cervical spine revealed heterotopic ossifications of the neck and thorax. Early diagnosis of FOP is vital because trauma, unnecessary biopsy and intramuscular injection are known to cause acceleration of heterotopic ossifications. Previous studies reported diffuse soft tissue swelling at the posterior neck, thoracic wall or paraspinal region as preosseous lesions of FOP (Shiva Kumar et al. Neurology. 2010;74(6):e20, Merchant et al. Pediatr Radiol. 2006;36(10):1108-11, Hagiwara et al. AJR Am J Roentgenol. 2003;181(4):1145-7). To our knowledge, diffuse soft tissue swelling of the scalp as a preosseous lesion of FOP and associated MRI findings have not yet been reported. We believe that awareness of preosseous lesions presenting as diffuse soft tissue swelling, in addition to shortening and valgus deformity of the great toes, is an important diagnostic clue for establishing FOP.


Assuntos
Imageamento por Ressonância Magnética , Miosite Ossificante/diagnóstico por imagem , Ossificação Heterotópica/diagnóstico por imagem , Couro Cabeludo/patologia , Feminino , Humanos , Lactente , Radiografia
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