RESUMEN
ß-mangostin is a dietary xanthone that has been reported to have the anticancer properties in some human cancer cell types. However, the antimetastatic effect and molecular mechanism of ß-mangostin action in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we found that ß-mangostin did not induce cytotoxicity in human HCC cells (SK-Hep-1, Huh-7 and HA22T/VGH cells). ß-mangostin could inhibit migration and invasion of human HCC cells. Meanwhile, ß-mangostin significantly decreased the protein activities and expression of matrix metalloproteinase (MMP)-2 and MMP-9 via increasing the activation of MEK1/2, ERK1/2, MEK4 and JNK1/2 signaling pathways. Furthermore, using specific inhibitor for ERK1/2 (PD98059) and JNK1/2 (JNKII) significantly restored the expression of MMP-2/-9 and invasion by ß-mangostin treatment in Huh-7 cells. In addition, ß-mangostin effectively restored the protein levels and transcription activity of MMP-2 and MMP-9 in siERK or siJNK-transfected Huh-7 cells, concomitantly with promotion on cell migration and invasion. Taken together, these findings are the first to demonstrate the antimetastatic activity of ß-mangostin against human HCC cells, which may act as a promising therapeutic agent for the treatment of HCC.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Xantonas/farmacología , Carcinoma Hepatocelular , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Humanos , Neoplasias Hepáticas , Sistema de Señalización de MAP Quinasas , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Invasividad NeoplásicaRESUMEN
OBJECTIVE: Rett syndrome (RTT) is characterized by neurological regression. This pioneering study investigated the effect of age on brain volume reduction by analyzing magnetic resonance imaging findings in participants with RTT, ranging from toddlers to adults. METHODS: Functional evaluation and neuroimaging were performed. All scans were acquired using a Siemens Tim Trio 3 T scanner with a 32-channel head coil. RESULTS: The total intracranial volume and cerebral white matter volume significantly increased with age in the control group compared with that in the RTT group (p < 0.05). Cortical gray matter volume reduction in the RTT group continued to increase in bilateral parietal lobes and left occipital lobes (p < 0.05). The differences in cortical gray matter volume between typically developing brain and RTT-affected brain may tend to continuously increase until adulthood in both temporal lobes although not significant after correction for multiple comparison. CONCLUSIONS: A significant reduction in brain volume was observed in the RTT group. Cortical gray matter volume in the RTT group continued to reduce in bilateral parietal lobes and left occipital lobes. These results provide a baseline for future studies on the effect of RTT treatment and related neuroscience research.
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Encéfalo , Imagen por Resonancia Magnética , Síndrome de Rett , Humanos , Síndrome de Rett/diagnóstico por imagen , Síndrome de Rett/fisiopatología , Síndrome de Rett/patología , Femenino , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/crecimiento & desarrollo , Adulto , Niño , Adulto Joven , Preescolar , Adolescente , Taiwán , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Masculino , Tamaño de los Órganos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
Protodioscin (PD) is a steroidal saponin with various pharmacological activities, including neuro-protective, anti-inflammatory, and anti-tumor activities. However, the effect of PD on human osteosarcoma (OS) cells is unclear. In this study, we found that PD significantly inhibits the growth of human HOS and 143B OS cells through the upregulation of apoptotic-related proteins (cleaved caspase-3, cleaved caspase-9, and cleaved PARP) and mitophagy-related proteins (LC3B and NIX), which contribute to the induction of apoptosis, and MMP (mitochondrial membrane potential) dysfunction and mitophagy. The inhibition of LC3 or NIX was shown to decrease apoptosis and mitophagy in PD-treated OS cells. The knockdown of p38MAPK by siRNA decreased mitochondrial dysfunction, autophagy, mitophagy, and the NIX/LC3B expression in the PD-treated OS cells. A binding affinity analysis revealed that the smaller the KD value (-7.6 Kcal/mol and -8.9 Kcal/mol, respectively), the greater the binding affinity in the PD-NIX and PD-LC3 complexes. These findings show the inhibitory effects of PD-induced mitophagy in human OS cells and may represent a novel therapeutic strategy for human OS, by targeting the NIX/LC3 pathways.
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Neoplasias Óseas , Osteosarcoma , Saponinas , Humanos , Neoplasias Óseas/tratamiento farmacológico , Mitofagia/genética , Osteosarcoma/tratamiento farmacológico , Proteínas Quinasas p38 Activadas por Mitógenos , Saponinas/farmacologíaRESUMEN
Recently, to conduct preclinical imaging research on clinical MRI systems has become an attractive alternative to researchers due to its wide availability, cost, and translational application to clinical human studies when compared to dedicated small animal, high-field preclinical MRI. However, insufficient signal-to-noise ratio (SNR) significantly degrades the applicability of those applications which require high SNR, e.g. magnetic resonance guided high-intensity focused ultrasound (MRgHIFU) treatment. This study introduces a wireless inductively coupled surface (WICS) coil design used on a clinical 3 T MRI system for MRgHIFU ablation. To evaluate the SNR improvement and temperature accuracy of WICS coil, the ex vivo experiments were performed on the pork tenderloins (n = 7) and the hind legs of deceased Sprague-Dawley rats (n = 5). To demonstrate the feasibility, the in vivo experiments were performed on the hind leg of Sprague-Dawley rat (n = 1). For all experiments, temperature measurements were performed before and during HIFU ablation. Temperature curves with and without WICS coil were compared to evaluate the temperature precision in ex vivo experiments. The use of WICS coil improves the temperature accuracy from 0.85 to 0.14 °C, demonstrating the feasibility of performing small animal MRgHIFU experiments using clinical 3 T MRI system with WICS coil.
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Ultrasonido Enfocado de Alta Intensidad de Ablación , Roedores , Ratas , Animales , Humanos , Estudios de Factibilidad , Ratas Sprague-Dawley , Imagen por Resonancia Magnética/métodos , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodosRESUMEN
BACKGROUND: Asiatic acid (AA) is a naturally pentacyclic triterpenoids extracted from traditional medicine Centella asiatica l. that has demonstrated possesses potential health benefits and antitumor ability. However, the precise anticancer effects and mechanisms by which AA impact RCC cells remains unclear. METHODS: Cell proliferation and cell cycle distribution were detected by MTT, colony formation assay and PI stain by flow cytometry, respectively. Cell mobility and invasiveness were determined by in vitro migration and invasion assay. The secretory MMP15 was detected by ELISA assay. Quantitative RT-PCR, siRNA, and immunoblot were used to determine gene expression/regulation and protein expression, respectively. Antimetastatic effect of AA were performed to lung nodule numbers in vivo metastasis mice model. MMP15, pERK1/2 and p-p38MAPK expressions were determined by immunohistochemistry. RESULTS: Our findings indicated cell proliferation and cell cycle distribution of RCC cells were not significantly influenced by AA treatment. AA suppressed cell migration, invasion and significantly down-regulated mRNA and protein expression of MMP-15 (Matrix Metallopeptidase-15). Activation of ERK1/2 and p38MAPK were inhibited with AA, whereas combined AA with siRNA-ERK or siRNA-p38MAPK markedly reduced the metastatic effect and decreased MMP-15 expression in 786-O and A498 cells. Finally, AA significantly reduced the lung metastasis formation and metastasis-related proteins of human 786-O cells in vivo metastasis mice model. CONCLUSION: AA inhibits the metastatic properties of RCC cells via inhibition of the p-ERK/p-p38MAPK axis and the subsequent down-regulation of MMP-15 in vitro and in vivo. Further study of AA as a potential anti-metastatic agent for RCC is warranted.
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Carcinoma de Células Renales , Centella , Neoplasias Renales , Triterpenos , Animales , Carcinoma de Células Renales/tratamiento farmacológico , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Centella/química , Femenino , Humanos , Neoplasias Renales/metabolismo , Masculino , Metaloproteinasa 15 de la Matriz , Ratones , Triterpenos Pentacíclicos , ARN Interferente Pequeño/farmacología , Triterpenos/farmacología , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
PURPOSE: We present a novel background tissue phase removing method, called anatomical phase extraction (APE), and to investigate the accuracy of temperature estimation and capability of reducing background artifacts compared with the conventional referenceless methods. METHODS: Susceptibility variance was acquired by subtracting pretreatment baseline images taken at different locations (nine pretreatment baselines are acquired and called φ 1 to φ 9). The susceptibility phase data φ S was obtained using the Wiener deconvolution algorithm. The background phase data φ T was isolated by subtracting φ S from the whole phase data. Finally, φ T was subtracted from the whole phase data before applying the referenceless method. As a proof of concept, the proposed APE method was performed on ex vivo pork tenderloin and compared with other two referenceless temperature estimation approaches, including reweighted â1 referenceless (RW- â1) and â2 referenceless methods. The proposed APE method was performed with four different baselines combination, namely, (φ 1, φ 5, φ 2, φ 4), (φ 3, φ 5, φ 2, φ 6), (φ 7, φ 5, φ 8, φ 4), and (φ 9, φ 5, φ 8, φ 6), and called APE experiment 1 to 4, respectively. The multibaseline method was used as a standard reference. The mean absolute error (MAE) and two-sample t-test analysis in temperature estimation of three regions of interest (ROI) between the multibaseline method and the other three methods, i.e., APE, RW- â1, and â2, were calculated and compared. RESULTS: Our results show that the mean temperature errors of the APE method-experiment 1, APE method-experiment 2, APE method-experiment 3, APE method-experiment 4, and RW- â1 and â2 referenceless method are 1.02°C, 1.04°C, 1.00°C, 1.00°C, 4.75°C, and 13.65°C, respectively. The MAEs of the RW- â1 and â2 referenceless methods were higher than that of APE method. The APE method showed no significant difference (p > 0.05), compared with the multibaseline method. CONCLUSION: The present work demonstrates the use of the APE method on referenceless MR thermometry to improve the accuracy of temperature estimation during MRI guided high-intensity focused ultrasound for ablation treatment.
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Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Termometría/métodos , Procedimientos Quirúrgicos Ultrasónicos/métodos , Algoritmos , Animales , Biología Computacional , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Humanos , Técnicas In Vitro , Fantasmas de Imagen , Sus scrofa , Temperatura , Termografía/métodosRESUMEN
Individuals with Rett syndrome (RTT) commonly demonstrate Parkinsonian features and dystonia at teen age; however, the pathological reason remains unclear. Abnormal iron accumulation in deep gray matter were reported in some Parkinsonian-related disorders. In this study, we investigated the iron accumulation in deep gray matter of RTT and its correlation with dystonia severity. We recruited 18 RTT-diagnosed participants with MECP2 mutations, from age 4 to 28, and 28 age-gender matched controls and investigated the iron accumulation by susceptibility weighted image (SWI) in substantia nigra (SN), globus pallidus (GP), putamen, caudate nucleus, and thalamus. Pearson's correlation was applied for the relation between iron accumulation and dystonia severity. In RTT, the severity of dystonia scales showed significant increase in subjects older than 10 years, and the contrast ratios of SWI also showed significant differences in putamen, caudate nucleus and the average values of SN, putamen, and GP between RTT and controls. The age demonstrated moderate to high negative correlations with contrast ratios. The dystonia scales were correlated with the average contrast ratio of SN, putamen and GP, indicating iron accumulation in dopaminergic system and related grey matter. As the first SWI study for RTT individuals, we found increased iron deposition in dopaminergic system and related grey matter, which may partly explain the gradually increased dystonia.
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Trastornos Distónicos/metabolismo , Sobrecarga de Hierro/metabolismo , Hierro/metabolismo , Síndrome de Rett/metabolismo , Adolescente , Adulto , Mapeo Encefálico/métodos , Estudios de Casos y Controles , Niño , Preescolar , Trastornos Distónicos/patología , Femenino , Sustancia Gris/metabolismo , Sustancia Gris/patología , Humanos , Sobrecarga de Hierro/genética , Sobrecarga de Hierro/patología , Imagen por Resonancia Magnética/métodos , Proteína 2 de Unión a Metil-CpG/genética , Mutación , Síndrome de Rett/genética , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Licochalcone A (LicA) has been reported to possess antitumor properties. However, its effect on human glioma cells remains unknown. In this study, we observed that LicA significantly suppressed the ADAM9 expression and the migration and invasion activities of human glioma cells (M059K, U-251 MG, and GBM8901) and exhibited no cell cytotoxicity. The human proteinase antibody array and immunoblot analysis indicated that the LicA treatment inhibited the expression of ADAM9 protein in human glioma cells. Recombinant human ADAM-9 (Rh-ADAM9) treatment significantly reversed the LicA-induced reduction in the ADAM9 level and the migration and invasion activities of human glioma cells. Additionally, the phosphorylation/activation of the mitogen-activated protein kinase kinase (MEK)-extracellularly responsive kinases (ERK) signaling pathway was significantly suppressed in LicA-treated human glioma cells. Cotreatment with LicA and PD98059 synergistically inhibited the ADAM9 expression, cell migration, and cell invasion, which suggested that the MEK-ERK signaling pathway was involved in the LicA-induced inhibition of the ADAM9 expression and the invasion activity of human glioma cells. These findings are the first evidence of LicA's anti-invasive properties against human glioma cells.
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Proteínas ADAM/metabolismo , Antineoplásicos/farmacología , Chalconas/farmacología , Glioma/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Proteínas ADAM/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glioma/genética , Glioma/patología , Glioma/fisiopatología , Humanos , Quinasas Quinasa Quinasa PAM/genética , Quinasas Quinasa Quinasa PAM/metabolismo , Proteínas de la Membrana/genética , Invasividad Neoplásica , Fosforilación/efectos de los fármacosRESUMEN
The advancement of information technology in financial applications nowadays have led to fast market-driven events that prompt flash decision-making and actions issued by computer algorithms. As a result, today's markets experience intense activity in the highly dynamic environment where trading systems respond to others at a much faster pace than before. This new breed of technology involves the implementation of high-speed trading strategies which generate significant portion of activity in the financial markets and present researchers with a wealth of information not available in traditional low-speed trading environments. In this study, we aim at developing feasible computational intelligence methodologies, particularly genetic algorithms (GA), to shed light on high-speed trading research using price data of stocks on the microscopic level. Our empirical results show that the proposed GA-based system is able to improve the accuracy of the prediction significantly for price movement, and we expect this GA-based methodology to advance the current state of research for high-speed trading and other relevant financial applications.
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Algoritmos , Inteligencia Artificial , Comercio , Ambiente , Inversiones en Salud , Comercio/economía , Comercio/métodos , Comercio/tendencias , Predicción , Humanos , Inversiones en Salud/economía , Modelos Económicos , TaiwánRESUMEN
Pairs trading is an important and challenging research area in computational finance, in which pairs of stocks are bought and sold in pair combinations for arbitrage opportunities. Traditional methods that solve this set of problems mostly rely on statistical methods such as regression. In contrast to the statistical approaches, recent advances in computational intelligence (CI) are leading to promising opportunities for solving problems in the financial applications more effectively. In this paper, we present a novel methodology for pairs trading using genetic algorithms (GA). Our results showed that the GA-based models are able to significantly outperform the benchmark and our proposed method is capable of generating robust models to tackle the dynamic characteristics in the financial application studied. Based upon the promising results obtained, we expect this GA-based method to advance the research in computational intelligence for finance and provide an effective solution to pairs trading for investment in practice.
Asunto(s)
Algoritmos , Inversiones en Salud/estadística & datos numéricos , Modelos Genéticos , Inteligencia Artificial , Inversiones en Salud/economíaRESUMEN
OBJECTIVE: Thyroid surgery is generally a safe surgery but its complications are still common. We wish to identify preoperative factors that predict postoperative complications. METHODS: A nationwide survey was conducted by senior surgeons from 16 medical centers and 5 regional hospitals in Taiwan to thyroid operations performed over 3 years. 3846 cases were retrospectively examined to identify factors influencing complications: indication for surgery, preoperative evaluation, such as ultrasonography, chest X-ray, computed tomography and magnetic resonance imaging, isotope scanning, fine-needle aspiration cytology (FNAC) and thyroid function test, and patient characteristics. RESULTS: Eighty-four percent of patients were female. Seven percent of the patients had immediate postoperative hypocalcemia (mild and severe) and 2.3%, hoarseness (recurrent laryngeal nerve (RLN) injury, temporary/permanent). Logistic regression analysis identified an association between hypocalcemia and RLN injury with age, hospital category, surgical procedure types (total thyroidectomy, unilateral, bilateral subtotal or total resection). A lower incidence of hypocalcemia was related to preoperative neck ultrasound and FNAC analysis (the odds ratio (OR) = 0.5 and 0.65, [95% confidence interval (CI) 0.331-0.768 and 0.459-0.911], P = 0.0014 and 0.0127, respectively), while RLN injury was not associated with any preoperative evaluation. The ORs of hypocalcemia and RLN injury for patients older than 50 years were 0.55 and 2.15, [0.393-0.763 and 1.356-3.4], P < 0.001 and 0.0012, respectively. CONCLUSIONS: The success of thyroid surgery depends on careful preoperative planning, including a preoperative neck ultrasound to determine the proximity of the nodule to the recurrent laryngeal nerve course, and the consideration of the type of anesthesia, adjuvant devices for intra-op monitoring of the RLN, and surgical modalities. Our results suggest that preoperative evaluation implementations are positively associated with strategy of surgery and postoperative hypocalcemia prevention.
RESUMEN
Evolutionary algorithms rarely deal with ontogenetic, non-inherited alteration of genetic information because they are based on a direct genotype-phenotype mapping. In contrast, several processes have been discovered in nature which alter genetic information encoded in DNA before it is translated into amino-acid chains. Ontogenetically altered genetic information is not inherited but extensively used in regulation and development of phenotypes, giving organisms the ability to, in a sense, re-program their genotypes according to environmental cues. An example of post-transcriptional alteration of gene-encoding sequences is the process of RNA Editing. Here we introduce a novel Agent-based model of genotype editing and a computational study of its evolutionary performance in static and dynamic environments. This model builds on our previous Genetic Algorithm with Editing, but presents a fundamentally novel architecture in which coding and non-coding genetic components are allowed to co-evolve. Our goals are: (1) to study the role of RNA Editing regulation in the evolutionary process, (2) to understand how genotype editing leads to a different, and novel evolutionary search algorithm, and (3) the conditions under which genotype editing improves the optimization performance of traditional evolutionary algorithms. We show that genotype editing allows evolving agents to perform better in several classes of fitness functions, both in static and dynamic environments. We also present evidence that the indirect genotype/phenotype mapping resulting from genotype editing leads to a better exploration/exploitation compromise of the search process. Therefore, we show that our biologically-inspired model of genotype editing can be used to both facilitate understanding of the evolutionary role of RNA regulation based on genotype editing in biology, and advance the current state of research in Evolutionary Computation.