RESUMEN
MOTIVATION: Light-field microscopy (LFM) is a compact solution to high-speed 3D fluorescence imaging. Usually, we need to do 3D deconvolution to the captured raw data. Although there are deep neural network methods that can accelerate the reconstruction process, the model is not universally applicable for all system parameters. Here, we develop AutoDeconJ, a GPU-accelerated ImageJ plugin for 4.4× faster and more accurate deconvolution of LFM data. We further propose an image quality metric for the deconvolution process, aiding in automatically determining the optimal number of iterations with higher reconstruction accuracy and fewer artifacts. RESULTS: Our proposed method outperforms state-of-the-art light-field deconvolution methods in reconstruction time and optimal iteration numbers prediction capability. It shows better universality of different light-field point spread function (PSF) parameters than the deep learning method. The fast, accurate and general reconstruction performance for different PSF parameters suggests its potential for mass 3D reconstruction of LFM data. AVAILABILITY AND IMPLEMENTATION: The codes, the documentation and example data are available on an open source at: https://github.com/Onetism/AutoDeconJ.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Microscopía/métodos , Redes Neurales de la ComputaciónRESUMEN
A Gram-stain-negative, strictly aerobic, non-motile, catalase- and oxidase-positive, pink and rod-shaped strain, designated RY-2T, was isolated from sediment of Fuyang River located in Wuqiang County, Hengshui City, Hebei Province, PR China. The strain grew at 25-45 °C (optimum, 37 °C), pH 7.0-8.0 (optimum, pH 7.0) and in the presence of 0-1.5â% (w/v) NaCl (optimum, 1â%). From the phylogenetic analysis of the 16S rRNA gene sequence, strain RY-2T was affiliated to the genus Mariniradius, and had the highest 16S rRNA gene sequence similarity to Mariniradius saccharolyticus JCM 17389T (98.3â%) and the similarity values between strain RY-2T and other type strains was all below 89.3â%. The genome size of strain RY-2T was 4.75 Mb and the DNA G+C content was 46.6â%. Values of digital DNA-DNA hybridization and average nucleotide identity between strain RY-2T and the reference strain were 63.2 and 95.5â%, respectively. The major fatty acids (≥5.0â%) were iso-C15â:â0 (37.9â%), summed feature 9 (8.4â%, iso-C17â:â1 ω9c and/or C16â:â010-methyl), anteiso-C15â:â0 (8.2â%), iso-C17â:â0 3-OH (7.6â%) and summed feature 4 (5.2â%, iso-C17â:â1 I and/or anteiso-C17â:â1 B) and its sole menaquinone was MK-7. The polar lipids consisted of phosphatidylethanolamine, an unknown phosphoglycolipid, an unidentified phospholipid, two unidentified aminolipids, three unidentified glycolipids and nine unidentified lipids. Based on the results of biochemical, physiological, phylogenomic and chemotaxonomic analyses, strain RY-2T is considered to represent a novel species of the genus Mariniradius within the family Cyclobacteriaceae, for which the name Mariniradius sediminis sp. nov. is proposed. The type strain is RY-2T (=GDMCC 1.2781T=JCM 35631T).
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Ácidos Grasos , Ríos , Ácidos Grasos/química , Filogenia , ARN Ribosómico 16S/genética , Xenobióticos , ADN Bacteriano/genética , Composición de Base , Técnicas de Tipificación Bacteriana , Análisis de Secuencia de ADN , Fosfolípidos/química , Vitamina K 2/químicaRESUMEN
Metal-organic frameworks (MOFs) are promising adsorbents for the removal of arsenic (As) from wastewater. The As removal efficiency is influenced by several factors, such as the textural properties of MOFs, adsorption conditions, and As species. Examining all of the relevant factors through traditional experiments is challenging. To predict the As adsorption capacities of MOFs toward organic, inorganic, and total As and reveal the adsorption mechanisms, four machine learning-based models were developed, with the adsorption conditions, MOF properties, and characteristics of different As species as inputs. The results demonstrated that the extreme gradient boosting (XGBoost) model exhibited the best predictive performance (test R2 = 0.93-0.96). The validation experiments demonstrated the high accuracy of the inorganic As-based XGBoost model. The feature importance analysis showed that the concentration of As, the surface area of MOFs, and the pH of the solution were the three key factors governing inorganic-As adsorption, while those governing organic-As adsorption were the concentration of As, the pHpzc value of MOFs, and the oxidation state of the metal clusters. The formation of coordination complexes between As and MOFs is possibly the major adsorption mechanism for both inorganic and organic As. However, electrostatic interaction may have a greater effect on organic-As adsorption than on inorganic-As adsorption. Overall, this study provides a new strategy for evaluating As adsorption on MOFs and discovering the underlying decisive factors and adsorption mechanisms, thereby facilitating the investigation of As wastewater treatment.
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Arsénico , Estructuras Metalorgánicas , Estructuras Metalorgánicas/química , Adsorción , Metales , Aprendizaje AutomáticoRESUMEN
BACKGROUND & AIMS: Dysregulation of microRNA (miRNA) expression in various cancers and their vital roles in malignant progression of cancers are well investigated. Our previous studies have analysed miRNAs that promote malignant progression in hepatocellular carcinoma (HCC); this study aims to systematically elucidate the mechanism of metastasis suppressor miRNAs in HCC. METHODS: High-throughput RNA sequencing was used to identify anti-metastatic miRNAs. The relative expression levels of miRNAs were confirmed by qRT-PCR. The biological functions of miRNAs were detected in vitro and in vivo. Circulating tumour cells (CTCs) were enriched from blood samples of HCC patients and cultured by three-dimensional (3D) system. Kaplan-Meier and Cox regression were used to analyse the value of potential target mRNAs on overall survival. RESULTS: miR-2392 was significantly down-regulated in HCC. Overexpression of miR-2392 suppressed proliferation, clonogenicity, mobility, spheroid formation and maintenance of cancer stem cells (CSC)-like characteristics in HCC cells. CTCs from HCC patients with lower serum miR-2392 level had stronger cell spheroid formation ability. A negative correlation between the content of miR-2392 in serum and the number of CTC spheroids had been found. We identified Jagged2 (JAG2) as a direct target of miR-2392. miR-2392 inhibited the expression of JAG2 by targeting 3'-UTR of JAG2. Down-regulation of JAG2 inhibited the overexpression effects of miR-2392 in vitro and in vivo. JAG2 is highly expressed in HCC and is closely related to poor prognosis and survival of patients. CONCLUSIONS: miR-2392 may play a role as a tumour suppressor to guide the individualized precise treatment of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Proteína Jagged-2/genética , Proteína Jagged-2/metabolismo , Neoplasias Hepáticas/patología , MicroARNs/metabolismoRESUMEN
Tumor microenvironment (TME) is a critical determinant for hepatocellular carcinoma (HCC). Hepatic stellate cells (HSCs) are main interstitial cells in TME and play a vital role in early intrahepatic invasion and metastasis of HCC. The potential mechanism on the interactions between HSCs and HCC cells remains unclear. In this study, the effects of extracellular vesicles (EVs)-derived OncomiRs that mediate communication between HCC cells and cancer-associated hepatic stellate cells (caHSCs) and remold TME were investigated. The results found that the HCC cells-released EVs contained more various OncomiRs, which could activate HSCs (LX2 cells) and transform them to caHSCs, the caHSCs in turn exerted promotion effects on HCC cells through HSCs-released EVs. To further simulate the effects of OncomiRs in EVs on construction of pro-metastatic TME, a group of OncomiRs, miR-21, miR-221 and miR-151 was transfected into HCC cells and LX2 cells. These microRNAs in the EVs from OncomiRs-enhanced cells were demonstrated to have oncogenic effects on HCC cells by upregulating the activities of protein kinase B (AKT)/extracellular signal-regulated kinase (ERK) signal pathways. Equivalent results were also found in HCC xenografted tumor models. The findings suggested that the OncomiR secretion and transference by cancer cells-released EVs can mediate the communication between HCC cells and HSCs. HCC cells and caHSCs, as well as their secreted EVs, jointly construct a pro-metastatic TME suitable for invasion and metastasis of cancer cells, all these TME components form a positive feedback loop to promote HCC progression and metastasis.
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Carcinoma Hepatocelular/genética , Comunicación Celular/genética , Neoplasias Hepáticas/genética , MicroARNs/metabolismo , Microambiente Tumoral/genética , Animales , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Vesículas Extracelulares/metabolismo , Regulación Neoplásica de la Expresión Génica , Células Estrelladas Hepáticas/citología , Células Estrelladas Hepáticas/patología , Humanos , Hígado/citología , Hígado/patología , Neoplasias Hepáticas/patología , Sistema de Señalización de MAP Quinasas/genética , Masculino , Ratones , Invasividad Neoplásica/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Much evidence suggested that cholesterol, eicosanoid and phospholipid metabolism plays crucial roles in inflammation, atherosclerosis, carcinogenesis, etc. Therefore, fast and accurate quantification of the metabolites in these metabolic pathways is necessary for discovering the molecular mechanisms and biomarkers of related diseases. In this assay, ultra-high performance liquid chromatography combined with triple quadrupole mass spectrometry platform (UPLC-QqQ-MS) based protocols were developed to simultaneously quantify a total of 104 key metabolites including 32 phospholipids (PLs), 44 eicosanoids (EAs), 28 oxysterols and bile acids (BAs), within 15 minutes. Validation results showed that this method is stable, sensitive and accurate for analyzing different matrix samples. Next, this method was used to characterize the metabolic phenotype of a CCl4-induced liver injury model. The results showed that polyunsaturated fatty acids (PUFA) and PUFA acyl-phospholipids (PFA-PLs) were down-regulated and the levels of saturated fatty acyl-phospholipids (SFA-PLs) and EAs were up-regulated in both the liver tissue and plasma of the CCl4-injury group. BAs were up-regulated in plasma, but down-regulated in the liver tissue of the CCl4-injury group. Immunohistochemistry assay demonstrated that the expression levels of cytosolic phospholipase A2 (cPLA2), phosphorylated cytosolic phospholipase A2 (p-cPLA2), secreted phospholipase A2-IIA (sPLA2-IIA) and lysophosphatidylcholine acyltransferase 1 (LPCAT1) were all up-regulated. According to our results, we drew a diagram of the CCl4-induced acute liver injury molecular mechanism. Moreover, we found that the area under the receiver operating characteristic curve (AUC) of 7α-hydroxycholesterol and 7ß-hydroxycholesterol was 1.0, which indicates that the two metabolites have significant potential for the diagnosis of acute liver injury. The outstanding performance of this analytical method proves its further usefulness for mechanism studies and biomarker screening of related diseases.
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Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Colesterol/metabolismo , Eicosanoides/metabolismo , Metabolómica/métodos , Fosfolípidos/metabolismo , Animales , Modelos Animales de Enfermedad , MasculinoRESUMEN
CD147 is highly expressed in hepatocellular carcinoma (HCC) and associated with the invasion and metastasis of HCC. The efficacy of I131 -metuximab (I131 -mab), a newly developed agent that targets CD147, as a radio-immunotherapy for local HCC, has been validated in clinical practice. However, the synergistic anticancer activity and molecular mechanism of different conjugated components within I131 -mab remain unclear. In this study, the cytological experiments proved that I131 -mab inhibited the proliferation and invasion of HCC cells. Mechanically, this inhibition effect was mainly mediated by the antibody component part of I131 -mab, which could reverse the epithelial-mesenchymal transition of HCC cells partially by suppressing the phosphorylation of VEGFR-2. The inhibitory effect of I131 on HCC cell proliferation and invasion is limited, whereas, when combined with metuximab, I131 significantly enhanced the sensitivity of HCC cells to CD147-mab and consequently reinforced the anticancer effects of CD147-mab, suggesting that the two components of I131 -mab exerted synergistic anti-HCC capability. Furthermore, the experiments using SMMC-7721 human HCC xenografts in athymic nude mice showed that I131 -mab and CD147-mab significantly inhibited the growth of xenograft tumors and that I131 -mab was more effective than CD147-mab. In conclusion, our results elucidated the mechanism underlying the anti-HCC effects of I131 -mab and provided a theoretical foundation for the clinical application of I131 -mab.
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Anticuerpos Monoclonales/farmacología , Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Transición Epitelial-Mesenquimal/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fosforilación , Células Tumorales Cultivadas , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The initial emittable concentration, Cm,0, the material phase diffusion coefficient, Dm, and the air/material partition coefficient, K, are the key parameters used to predict the formaldehyde emissions from indoor building materials. This work presents formaldehyde emission experiments of plywood panels in a climatic chamber under various environmental conditions, which provides information on how relative humidity, temperature, and loading degree affect the formaldehyde emission. The experimental results showed that formaldehyde concentration in the climatic chamber increased rapidly during the initial 3 h, and then reached equilibrium after 7 h. The equilibrium concentration of formaldehyde in the closed chamber was increased by 1.1-1.3 times with the relative humidity increased by 20%, and 1.3-2.5 times with the temperature increased by 5 °C, respectively. In agreement with the experimental treatment, a new method of estimating parameters was carried out in a theoretical model from formaldehyde emission, opening the way to a factorial analysis of the relevant parameters for relative humidity and temperature. The theoretical model with estimated parameters was further validated by experiments with different environmental conditions, which should help to quickly determine the parameters needed to predict formaldehyde emissions.
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Contaminación del Aire Interior/análisis , Materiales de Construcción/análisis , Formaldehído/análisis , Formaldehído/farmacocinética , Modelos Teóricos , Materiales de Construcción/efectos adversos , Difusión , Humedad , Ensayo de Materiales , Reproducibilidad de los Resultados , Estadística como Asunto , TemperaturaRESUMEN
Costunolide (CE) and dehydrocostuslactone (DE) are derived from many species of medicinal plants, such as Saussurea lappa Decne and Laurus nobilis L. They have been reported for their wide spectrum of biological effects, including anti-inflammatory, anticancer, antiviral, antimicrobial, antifungal, antioxidant, antidiabetic, antiulcer, and anthelmintic activities. In recent years, they have caused extensive interest in researchers due to their potential anti-cancer activities for various types of cancer, and their anti-cancer mechanisms, including causing cell cycle arrest, inducing apoptosis and differentiation, promoting the aggregation of microtubule protein, inhibiting the activity of telomerase, inhibiting metastasis and invasion, reversing multidrug resistance, restraining angiogenesis has been studied. This review will summarize anti-cancer activities and associated molecular mechanisms of these two compounds for the purpose of promoting their research and application.
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Antineoplásicos/farmacología , Lactonas/farmacología , Sesquiterpenos/farmacología , Inhibidores de la Angiogénesis/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , HumanosRESUMEN
Matrine (MT) and oxymatrine (OMT), two kinds of alkaloid components found in the roots of Sophora species, have various pharmacological activities and are demonstrated to have anti-inflammatory, anti-allergic, anti-virus, anti-fibrotic, and cardiovascular protective effects. They are recently proved to have anti-cancer potentials, such as inhibiting cancer cell proliferation, inducing cell cycle arrest, accelerating apoptosis, restraining angiogenesis, inducing cell differentiation, inhibiting cancer metastasis and invasion, reversing multidrug resistance, and preventing or reducing chemotherapy- or radiotherapy-induced toxicity when combined with other chemotherapeutic drugs. In this review, we summarize the recent investigations regarding the anti-cancer activities and possible molecular targets of MT and OMT for cancer prevention and treatment in order to provide clues and references for further study.
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Alcaloides/farmacología , Antineoplásicos/farmacología , Quinolizinas/farmacología , Inhibidores de la Angiogénesis/farmacología , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos , Humanos , Telomerasa/antagonistas & inhibidores , MatrinasRESUMEN
Published data regarding the association between the APE1 Asp148Glu polymorphism and breast cancer susceptibility showed inconclusive results. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. We systematically searched PubMed, Embase, Elsevier, and Springer for relevant articles published before December 10. 2013. The strength of association between APE1 Asp148Glu polymorphism and breast cancer susceptibility was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95% CI) using the software Stata (version 10.0). A total of 7 case-control studies including 3,460 cases and 3,909 controls were included for analysis. Overall, no significant associations were found between the APE1 Asp148Glu polymorphism and breast cancer susceptibility for GG vs TT (OR = 1.00, 95% CI = 0.87-1.14); TG vs TT (OR = 1.06, 95% CI = 0.95-1.18); the dominant model GG + TG vs TT (OR = 1.04, 95% CI = 0.94-1.16) and the recessive model GG vs TG + TT (OR = 0.99, 95% CI = 0.88-1.11). In subgroup analysis, a significant association was found for TG vs TT in Asian subgroup (OR = 1.17, 95% CI = 1.00 ~ 1.36) and in population-based subgroup (OR = 1.18, 95% CI = 1.00 ~ 1.38). This meta-analysis suggested that the APE1 Asp148Glu polymorphism was a risk factor for breast cancer susceptibility among Asian population.
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Neoplasias de la Mama/genética , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Sesgo de PublicaciónRESUMEN
The XRCC1 Arg194Trp and Arg280His polymorphisms are likely to be implicated with the development of head and neck cancer. However, studies of association have been inconsistent. This meta-analysis of the available literature was performed to make a more precise estimation of the risk associated with these polymorphisms. A comprehensive literature search was conducted to identify all case-control studies of the XRCC1 Arg194Trp and Arg280His polymorphisms in head and neck cancer. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. A total of 20 eligible studies were selected for this meta-analysis, including 3,362 cases and 5,796 controls for the XRCC1 Arg194Trp polymorphism and 1,932 cases and 2,757 controls for the XRCC1 Arg280His polymorphism. Overall, no significant associations were found in all genetic models when the studies were pooled into the meta-analysis for the Arg194Trp and Arg280His polymorphisms. When stratified by ethnicity, significant associations were found for Arg194Trp polymorphism in CT vs CC (OR = 1.26, 95% CI = 1.05-1.52) and the recessive model (OR = 1.28, 95% CI = 1.07-1.53) in Asian population, and no significant associations were found in non-Asian population in all genetic models. This meta-analysis suggests that the XRCC1 Arg194Trp polymorphism is a risk factor for head and neck cancer in Asian populations.
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Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Neoplasias de Cabeza y Cuello/genética , Polimorfismo Genético/genética , Estudios de Casos y Controles , Humanos , Pronóstico , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos XRESUMEN
The effect of purified Cry1Ca insecticidal protein on the growth of Chlorella pyrenoidosa was studied in a three-generation toxicity test. The C. pyrenoidosa medium with a density of 5.4 × 10(5) cells/mL was subcultured for three generations with added Cry1Ca at 0, 10, 100, and 1000 µg/L, and cell numbers were determined daily. To explore the distribution of Cry1Ca in C. pyrenoidosa and the culture medium, Cry1Ca was added at 1000 µg/L to algae with a high density of 4.8 × 10(6) cells/mL, and Cry1Ca content was determined daily in C. pyrenoidosa and the culture medium by enzyme-linked immunosorbent assays. Our results showed that the growth curves of C. pyrenoidosa exposed to 10, 100, and 1000 µg/L of Cry1Ca almost overlapped with that of the blank control, and there were no statistically significant differences among the four treatments from day 0 to day 7, regardless of generation. Moreover, the Cry1Ca content in the culture medium and in C. pyrenoidosa sharply decreased under exposure of 1000 µg/L Cry1Ca with high initial C. pyrenoidosa cell density. The above results demonstrate that Cry1Ca in water can be rapidly adsorbed and degraded by C. pyrenoidosa, but it has no suppressive or stimulative effect on algae growth.
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Proteínas Bacterianas/metabolismo , Chlorella/efectos de los fármacos , Chlorella/metabolismo , Endotoxinas/metabolismo , Proteínas Hemolisinas/metabolismo , Bacillus/química , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas/análisis , Proteínas Bacterianas/toxicidad , Chlorella/crecimiento & desarrollo , Medios de Cultivo/química , Endotoxinas/análisis , Endotoxinas/toxicidad , Ensayo de Inmunoadsorción Enzimática , Proteínas Hemolisinas/análisis , Proteínas Hemolisinas/toxicidad , Pruebas de Toxicidad , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/toxicidadRESUMEN
BACKGROUND: OCT4 and BIRC5 are preferentially expressed in human cancer cells and mediate cancer cell survival and tumor maintenance. However, the molecular mechanism that regulates OCT4 and BIRC5 expression is not well characterized. METHODS: By manipulating OCT4 and BIRC5 expression in hepatocellular carcinoma (HCC) cell lines, the regulatory mechanism of OCT4 on BIRC5 and CCND1 were investigated. RESULTS: Increasing or decreasing OCT4 expression could enhance or suppress BIRC5 expression, respectively, by regulating the activity of BIRC5 promoter. Because there is no binding site for OCT4 within BIRC5 promoter, the effect of OCT4 on BIRC5 promoter is indirect. An octamer motif for OCT4 in the CCND1 promoter has directly and partly participated in the regulation of CCND1 promoter activity, suggesting that OCT4 also could upregulated the expression of CCND1. Co-suppression of OCT4 and BIRC5 induced cancer cell apoptosis and cell cycle arrest, thereby efficiently inhibiting the proliferative activity of cancer cells and suppressing the growth of HCC xenogrfts in nude mice. CONCLUSION: OCT4 can upregulate BIRC5 and CCND1 expression by increasing their promoter activity. These factors collusively promotes HCC cell proliferation, and co-suppression of OCT4 and BIRC5 is potentially beneficial for HCC treatment.
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Carcinoma Hepatocelular/metabolismo , Ciclina D1/metabolismo , Proteínas Inhibidoras de la Apoptosis/metabolismo , Neoplasias Hepáticas Experimentales/metabolismo , Proteínas de Neoplasias/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/fisiología , Análisis de Varianza , Animales , Apoptosis/fisiología , Carcinoma Hepatocelular/patología , Puntos de Control del Ciclo Celular/fisiología , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas Experimentales/patología , Ratones , Ratones Endogámicos BALB C , Regiones Promotoras Genéticas , Survivin , Regulación hacia ArribaRESUMEN
AIM: There is no clear consensus on the optimal timing of surgical resection for synchronous colorectal liver metastases (SCLM). This study is a meta-analysis of the available evidence. METHODS: Systematic review and meta-analysis of trials comparing outcomes following simultaneous resection with staged resection for SCLM published from 1990 to 2010 in PubMed, Embase, Ovid and Medline. Pooled odds ratios (OR) or weighted mean differences (WMD) with 95% confidence intervals (95% CI) were calculated using either the fixed effects or random effects model. RESULTS: Nineteen non-randomized controlled trials (NRCT) studies were included in this analysis. These studies included a total of 2724 patients: 1116 underwent simultaneous resection and 1608 underwent staged resection. Meta-analysis showed that shorter hospital stay (P < 0.001) and lower total complication rate (P < 0.001) were observed in patients undergoing simultaneous resection group. The overall survival rate in the simultaneous resection group did not statistically differ with that in the staged resection group at 1 year (P = 0.13), 3 years (P = 0.26), 5 years (P = 0.38), as well as the 1, 3 and 5 years disease-free survival rates (respectively, P = 0.55; P = 0.16; P = 0.12). No significant difference was noted between the two groups in terms of mortality (P = 0.16), intraoperative blood loss (P = 0.06) and recurrence (P = 0.47). CONCLUSION: Simultaneous resection is safe and efficient in the treatment of patients with SCLM while avoiding a second laparotomy. In selected patients, simultaneous resection might be considered as the preferred approach. However, the findings have to be carefully interpreted due to the lower level of evidence and the existence of heterogeneity.
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AIM: The human sulfatase-1 (hSulf-1) gene regulates the sulfation of heparan sulfate proteoglycans (HSPG) and suppresses tumorigenesis and angiogenesis by inhibiting several growth factor signaling pathways. Because the serine-threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK) signaling pathways are critical in cell survival, proliferation, migration and angiogenesis, the possible correlation between hSulf-1 and AKT/ERK signaling in hepatocellular carcinoma (HCC) cells needs further exploration. METHODS: Adenovirus Ad5-hSulf1 carrying the hSulf-1 gene, and vectors carrying hSulf-1 shRNA, AKT shRNA and ERK shRNA were constructed and used to manipulate the expression of hSulf-1, AKT and ERK in SMMC-7721 cells. The scarification test, transwell and 3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide assays were used to examine the cellular migration and proliferation, and the expression of hSulf-1 and signaling factors, including the total and phosphorylated AKT and ERK, was analyzed by western blot in SMMC-7721 cells. RESULTS: After infection with Ad5-hSulf1, the expression of hSulf-1 was increased with viral multiplicity of infection in SMMC-7721 cells. Compared with the control adenovirus Ad5-EGFP and blank control groups, cells in the Ad5-hSulf1 group were showed that the phosphorylation of AKT and ERK was decreased. Meanwhile, the cell migration and cell viability were obviously suppressed. CONCLUSION: The expression of hSulf-1 mediated by adenovirus in HCC cells could downregulate the activity of AKT and ERK signaling pathways, and inhibit HCC cell migration and proliferation. The hSulf-1 gene may be considered as a candidate of antitumor factor for cancer gene therapy.
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Replication-competent adenovirus (RCAd) has been used extensively in cancer gene therapy, and tumor-selection is critical for the use of replication-competent adenovirus. Here we investigated the anti-tumor characterization of oncolytic virus, whose E1A gene is under the control of a renal cell carcinoma specific promoter - the G250 promoter. The constructed oncolytic virus G250-Ki67 is armed with transgene of Ki67-siRNA, and G250-ZD55-Ki67 also with E1B-55 KD deleted. The tumor-specific expression of E1A and Ki67 was demonstrated by Western blot and immunohistochemistry staining, and the tumor-specific cytotoxicity was assessed by crystal violet staining and cell viability assays. The G250-Ki67 and G250-ZD55-Ki67 adenoviruses could express E1A protein in 786-O and OSRC cell lines but not in ACHN and HK-2 cell lines. The expression of Ki67 gene in 786-O and OSRC cell lines were suppressed by these adenoviruses. The cytotoxic effects induced by G250-ZD55-Ki67 and G250-Ki67 were more obvious on the 786-O cell lines than on the OSRC cell lines. Each group of adenoviruses could inhibit the proliferation of the 786-O cells and OSRC cells. However, the effects induced by G250-ZD55-Ki67 and G250-Ki67 on 786-O cells were stronger than on OSRC cells. Moreover, G250-ZD55-Ki67 had enhanced antitumor activities in these renal cancer cells compared with G250-Ki67. G250 promoter-derived CRAds carrying Ki67-siRNA could highly amplify and express Ki67-siRNA in renal cancer cells with expression of G250 antigen, inhibit renal cancer cells proliferation and induce apoptosis. These results demonstrated that the G250-specific oncolytic adenovirus expressing Ki67-siRNA is applicable for human renal clear cell cancer therapy.
Asunto(s)
Antígenos de Neoplasias/genética , Anhidrasas Carbónicas/genética , Carcinoma de Células Renales/virología , Antígeno Ki-67/genética , Neoplasias Renales/virología , Viroterapia Oncolítica/métodos , Virus Oncolíticos/genética , Regiones Promotoras Genéticas , Adenoviridae/genética , Animales , Western Blotting , Anhidrasa Carbónica IX , Carcinoma de Células Renales/genética , Línea Celular Tumoral , Humanos , Inmunohistoquímica , Neoplasias Renales/genética , Ratones , Ratones Endogámicos BALB C , ARN Interferente Pequeño , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Hepatocyte injury is a common pathological cause of various liver diseases. Due to a lack of an effective preventive treatment, gene therapy has become an interesting approach to prevent and alleviate liver injury. AIMS: A protective effect of adenovirus-mediated dual gene expression of human interleukin-10 (hIL-10) and human hepatocyte growth factor (hHGF) was investigated against tetrachloromethane (CCl(4))-induced hepatocyte injury in rats. METHODS: An adenoviral vector carrying the hIL-10 and hHGF genes was constructed, and its protective effect against rat hepatocyte injury was investigated both in vivo and in vitro. RESULTS: In the in vitro CCl(4)-induced cell injury model, simultaneous transfection of hIL-10 and hHGF genes via an adenoviral vector resulted in production of anti-hepatocyte biological factors by an autocrine mechanism, then significantly improved hepatocyte viability. In the in vivo rat model, synergistic effects of these two gene products protected hepatocytes from damage by reducing the CC1(4)-induced hepatocyte degeneration, hepatic fibrosis, and intrahepatic inflammatory cell infiltration, thereby preserving liver function. CONCLUSION: Adenovirus-mediated dual gene expression of hIL-10 and hHGF effectively protected against liver damage by likely regulating immune responses to reduce hepatocyte injury and by promoting hepatocyte regeneration. The hIL-10 and hHGF dual gene expression vector has significant potential in the field of liver disease therapeutics and constitutes one of the most promising current strategies for gene therapy.
Asunto(s)
Adenoviridae/genética , Tetracloruro de Carbono/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Regulación Viral de la Expresión Génica/fisiología , Factor de Crecimiento de Hepatocito/fisiología , Interleucina-10/fisiología , Animales , Tetracloruro de Carbono/farmacología , Células Cultivadas , Modelos Animales de Enfermedad , Vectores Genéticos , Factor de Crecimiento de Hepatocito/genética , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Hepatocitos/fisiología , Humanos , Técnicas In Vitro , Interleucina-10/genética , Hígado/efectos de los fármacos , Hígado/patología , Hígado/fisiología , Masculino , Ratas , Ratas Sprague-Dawley , TransfecciónRESUMEN
OBJECTIVE: To investigate the relationship between p16 expression and cell proliferation and prognosis in gastric cancer patients. METHODS: Gastric cancer cell lines SGC-7901, MKN45, MKN28, human embryonic kidney cell line HEK293, human fibroblast cell line MRC-5, and surgical specimens of gastric carcinoma and adjacent normal gastric mucosa from 65 patients were included in this study. RT-PCR, MTT and FCM assays were used to detect p16 expression in gastric cancer cell lines and surgical specimens of gastric cancer. MTT assay was used to determine cancer cell viability and FCM to detect cell cycle. Kaplan-Meier survival curve and Log-Rank statistics were used to analyze the relationship between p16 expression and survival of petients with gastric cancer. RESULTS: Gastric cancer cell lines were mostly negative for p16 expression, and p16 was re-expressed after the cells transfected with p16 gene by adenovirus AdCMV-p16. p16 re-expression resulted in the decrease of cancer cell viability and cancer cell cycle arrest with increased G(1) phase and decreased S phase. p16 expression in cancer specimens was 32.3% (21/65), significantly lower than the 81.5% (53/65) in normal mucosa (χ(2) = 32.124, P < 0.001). The disease-free survival was significantly shorter in p16-negative patients than that in p16-positive patients (P < 0.01), but not the overall survival (P > 0.05). p16 expression was significantly correlated with differentiation and lymph node metastasis, but not significantly correlated with sex, age, tumor size or invasion depth of the gastric cancer. CONCLUSIONS: p16 gene is important for cancer cell proliferation. The inactivation gives cancer cells a high activity for proliferation and metastasis, and then influences the disease-free survival of gastric cancer patients.