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1.
Animals (Basel) ; 14(10)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38791710

RESUMEN

Fish fry counting has been vital in fish farming, but current computer-based methods are not feasible enough to accurately and efficiently calculate large number of fry in a single count due to severe occlusion, dense distribution and the small size of fish fry. To address this problem, we propose the deconvolution enhancement keypoint network (DEKNet), a method for fish fry counting that features a single-keypoint approach. This novel approach models the fish fry as a point located in the central part of the fish head, laying the foundation for our innovative counting strategy. To be specific, first, a fish fry feature extractor (FFE) characterized by parallel dual branches is designed for high-resolution representation. Next, two identical deconvolution modules (TDMs) are added to the generation head for a high-quality and high-resolution keypoint heatmap with the same resolution size as the input image, thus facilitating the precise counting of fish fry. Then, the local peak value of the heatmap is obtained as the keypoint of the fish fry, so the number of these keypoints with coordinate information equals the number of fry, and the coordinates of the keypoint can be used to locate the fry. Finally, FishFry-2023, a large-scale fish fry dataset, is constructed to evaluate the effectiveness of the method proposed by us. Experimental results show that an accuracy rate of 98.59% was accomplished in fish fry counting. Furthermore, DEKNet achieved a high degree of accuracy on the Penaeus dataset (98.51%) and an MAE of 13.32 on a public dataset known as Adipocyte Cells. The research outcomes reveal that DEKNet has superior comprehensive performance in counting accuracy, the number of parameters and computational effort.

2.
Animals (Basel) ; 13(12)2023 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-37370546

RESUMEN

Today, large-scale Penaeus monodon farms no longer incubate eggs but instead purchase larvae from large-scale hatcheries for rearing. The accurate counting of tens of thousands of larvae in these transactions is a challenging task due to the small size of the larvae and the highly congested scenes. To address this issue, we present the Penaeus Larvae Counting Strategy (PLCS), a simple and efficient method for counting Penaeus monodon larvae that only requires a smartphone to capture images without the need for any additional equipment. Our approach treats two different types of keypoints as equip keypoints based on keypoint regression to determine the number of shrimp larvae in the image. We constructed a high-resolution image dataset named Penaeus_1k using images captured by five smartphones. This dataset contains 1420 images of Penaeus monodon larvae and includes general annotations for three keypoints, making it suitable for density map counting, keypoint regression, and other methods. The effectiveness of the proposed method was evaluated on a real Penaeus monodon larvae dataset. The average accuracy of 720 images with seven different density groups in the test dataset was 93.79%, outperforming the classical density map algorithm and demonstrating the efficacy of the PLCS.

3.
Adv Exp Med Biol ; 1408: 291-308, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37093434

RESUMEN

Prostate-specific membrane antigen (PSMA) is expressed in epithelial cells of the prostate gland and is strongly upregulated in prostatic adenocarcinoma, with elevated expression correlating with metastasis, progression, and androgen independence. Because of its specificity, PSMA is a major target of prostate cancer therapy; however, detectable levels of PSMA are also found in other tissues, especially in salivary glands and kidney, generating bystander damage of these tissues. Antibody target therapy has been used with relative success in reducing tumor growth and prostate specific antigen (PSA) levels. However, since antibodies are highly stable in plasma, they have prolonged time in circulation and accumulate in organs with an affinity for antibodies such as bone marrow. For that reason, a second generation of PSMA targeted therapeutic agents has been developed. Small molecules and minibodies have had promising clinical trial results, but concerns about their specificity had arisen with side effects due to accumulation in salivary glands and kidneys. Herein we study the specificity of small molecules and minibodies that are currently being clinically tested. We observed a high affinity of these molecules for PSMA in prostate, kidney and salivary gland, suggesting that their effect is not prostate specific. The search for specific prostate target agents must continue so as to optimally treat patients with prostate cancer, while minimizing deleterious effects in other PSMA expressing tissues.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/patología , Antígenos de Superficie/metabolismo , Antígeno Prostático Específico
4.
BMC Geriatr ; 22(1): 460, 2022 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-35624415

RESUMEN

BACKGROUND: This study aimed to investigate the potential effect of preoperative frailty on postoperative clinical outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Data of patients aged 18 years and older who were diagnosed with subarachnoid hemorrhage or intracerebral hemorrhage, underwent aneurysm repair surgical intervention from 2005 to 2014. A retrospective database analysis was performed based on U.S. National Inpatient Sample (NIS) from 2005 to 2014. Frailty was determined using the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining diagnoses indicator. Patients were stratified into frail and non-frail groups and the study endpoints were incidence of postoperative complications and related adverse clinical outcomes. RESULTS: Among 20,527 included aSAH patients, 2303 (11.2%) were frail and 18,224 (88.8%) were non-frail. Significant differences were found between frailty and non-frailty groups in the four clinical outcomes (all p < 0.05). Multivariate analysis showed that frailty was associated with significant higher risks of discharge to institutional care (aOR: 2.50, 95%CI: 2.10-2.97), tracheostomy or gastrostomy tube replacement (aOR: 4.41, 95%CI: 3.81-5.10) and postoperative complications (aOR: 3.29, 95%CI: 2.55-4.25) but a lower risk of death in hospital (aOR: 0.40, 95%CI: 0.33-0.49) as compared with non-frailty. Stratified analysis showed the impact of frailty on some of the outcomes were greater among patients younger than 65 years than their older counterparts. CONCLUSIONS: Frailty is significantly correlated with the increased risk of discharge to institutional care, tracheostomy or gastrostomy tube placement, and postoperative complications but with the reduced risk of in-hospital mortality outcomes after aneurysm repair. Frailty seems to have greater impact among younger adults than older ones. Baseline frailty evaluation could be applied to risk stratification for aSAH patients who were undergoing surgery.


Asunto(s)
Fragilidad , Hemorragia Subaracnoidea , Fragilidad/complicaciones , Fragilidad/diagnóstico , Fragilidad/epidemiología , Humanos , Pacientes Internos , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Hemorragia Subaracnoidea/diagnóstico , Hemorragia Subaracnoidea/epidemiología , Hemorragia Subaracnoidea/cirugía
5.
Front Oncol ; 11: 674889, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34295815

RESUMEN

OBJECTIVES: Endoscopic nasopharyngectomy (ENPG) is a promising way in treating recurrent nasopharyngeal carcinoma (rNPC), but sometimes may require therapeutic internal carotid artery (ICA) occlusion beforehand. Balloon test occlusion (BTO) is performed to evaluate cerebral ischemic tolerance for ICA sacrifice. However, absence of neurological deficits during BTO does not preclude occur of delayed cerebral ischemia after permanent ICA occlusion. In this study, we evaluate the utility of near-infrared spectroscopy (NIRS) regional cerebral oxygen saturation (rSO2) monitoring during ICA BTO to quantify cerebral ischemic tolerance and to identify the valid cut-off values for safe carotid artery occlusion. This study also aims to find out angiographic findings of cerebral collateral circulation to predict ICA BTO results simultaneously. MATERIAL AND METHODS: 87 BTO of ICA were performed from November 2018 to November 2020 at authors' institution. 79 angiographies of collateral flow were performed in time during BTO and classified into several Subgroups and Types according to their anatomic and collateral flow configurations. 62 of 87 cases accepted monitoring of cerebral rSO2. Categorical variables were compared by using Fisher exact tests and Mann-Whitney U tests. Receiver operating characteristic curve analysis was used to determine the most suitable cut-off value. RESULTS: The most suitable cut-off △rSO2 value for detecting BTO-positive group obtained through ROC curve analysis was 5% (sensitivity: 100%, specificity: 86%). NIRS rSO2 monitoring wasn't able to detect BTO false-negative results (p = 0.310). The anterior Circle was functionally much more important than the posterior Circle among the primary collateral pathways. The presence of secondary collateral pathways was considered as a sign of deteriorated cerebral hemodynamic condition during ICA BTO. In Types 5 and 6, reverse blood flow to the ICA during BTO protected patients from delayed cerebral ischemia after therapeutic ICA occlusion (p = 0.0357). In Subgroup IV, absence of the posterior Circle was significantly associated with BTO-positive results (p = 0.0426). CONCLUSION: Angiography of cerebral collateral circulation during ICA BTO is significantly correlated with ICA BTO results. Angiographic ICA BTO can be performed in conjunction with NIRS cerebral oximeter for its advantage of being noninvasive, real-time, cost-effective, simple for operation and most importantly for its correct prediction of most rSO2 outcomes of ICA sacrifice. However, in order to ensure a safe carotid artery occlusion, more quantitative adjunctive blood flow measurements are recommended when angiography of cerebral collateral circulation doesn't fully support rSO2 outcome among clinically ICA BTO-negative cases.

6.
ACS Appl Mater Interfaces ; 13(15): 17207-17219, 2021 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-33845570

RESUMEN

Osteoclastic resorption of bones plays a central role in both osteoporosis and bone metastasis. A reliable in vitro assay that simulates osteoclastic resorption in vivo would significantly speed up the process of developing effective therapeutic solutions for those diseases. Here, we reported the development of a novel and robust nanostructured calcium phosphate coating with unique functions on the track-etched porous membrane by using an ammonia-induced mineralization (AiM) technique. The calcium phosphate coating uniformly covers one side of the PET membrane, enabling testing for osteoclastic resorption. The track-etched pores in the PET membrane allow calcium phosphate mineral pins to grow inside, which, on the one hand, enhances coating integration with a membrane substrate and, on the other hand, provides diffusion channels for delivering drugs from the lower chamber of a double-chamber cell culture system. The applications of the processed calcium phosphate coating were first demonstrated as a drug screening device by using alendronate, a widely used drug for osteoporosis. It was confirmed that the delivery of alendronate significantly decreased both the number of monocyte-differentiated osteoclasts and coating resorption. To demonstrate the application in studying bone metastasis, we delivered a PC3 prostate cancer-conditioned medium and confirmed that both the differentiation of monocytes into osteoclasts and the osteoclastic resorption of the calcium phosphate coating were significantly enhanced. This novel assay thus provides a new platform for studying osteoclastic activities and assessing drug efficacy in vitro.


Asunto(s)
Amoníaco/química , Huesos/patología , Fosfatos de Calcio/química , Nanoestructuras/química , Osteoporosis/fisiopatología , Alendronato/administración & dosificación , Alendronato/farmacología , Animales , Huesos/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Portadores de Fármacos/química , Humanos , Membranas Artificiales , Ratones , Osteoclastos/efectos de los fármacos , Osteoclastos/patología , Osteoporosis/metabolismo , Osteoporosis/patología , Células PC-3 , Porosidad , Células RAW 264.7
7.
Nat Commun ; 11(1): 3243, 2020 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-32591507

RESUMEN

Dysregulation of polyamine metabolism has been linked to the development of colorectal cancer (CRC), but the underlying mechanism is incompletely characterized. Here, we report that spermine synthase (SMS), a polyamine biosynthetic enzyme, is overexpressed in CRC. Targeted disruption of SMS in CRC cells results in spermidine accumulation, which inhibits FOXO3a acetylation and allows subsequent translocation to the nucleus to transcriptionally induce expression of the proapoptotic protein Bim. However, this induction is blunted by MYC-driven expression of miR-19a and miR-19b that repress Bim production. Pharmacological or genetic inhibition of MYC activity in SMS-depleted CRC cells dramatically induces Bim expression and apoptosis and causes tumor regression, but these effects are profoundly attenuated by silencing Bim. These findings uncover a key survival signal in CRC through convergent repression of Bim expression by distinct SMS- and MYC-mediated signaling pathways. Thus, combined inhibition of SMS and MYC signaling may be an effective therapy for CRC.


Asunto(s)
Proteína 11 Similar a Bcl2/metabolismo , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/patología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Espermina Sintasa/metabolismo , Acetilación/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Azepinas/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/genética , Regulación hacia Abajo/efectos de los fármacos , Femenino , Proteína Forkhead Box O3/metabolismo , Eliminación de Gen , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Modelos Biológicos , Poliaminas/metabolismo , Triazoles/farmacología , Regulación hacia Arriba/efectos de los fármacos
8.
Biomicrofluidics ; 13(1): 014110, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30867880

RESUMEN

Efforts to further improve the clinical management of prostate cancer (PCa) are hindered by delays in diagnosis of tumours and treatment deficiencies, as well as inaccurate prognoses that lead to unnecessary or inefficient treatments. The quantitative and qualitative analysis of circulating tumour cells (CTCs) may address these issues and could facilitate the selection of effective treatment courses and the discovery of new therapeutic targets. Therefore, there is much interest in isolation of elusive CTCs from blood. We introduce a microfluidic platform composed of a multiorifice flow fractionation (MOFF) filter cascaded to an integrated microfluidic magnetic (IMM) chip. The MOFF filter is primarily employed to enrich immunomagnetically labeled blood samples by size-based hydrodynamic removal of free magnetic beads that must originally be added to samples at disproportionately high concentrations to ensure the efficient immunomagnetic labeling of target cancer cells. The IMM chip is then utilized to capture prostate-specific membrane antigen-immunomagnetically labeled cancer cells from enriched samples. Our preclinical studies showed that the proposed method can selectively capture up to 75% of blood-borne PCa cells at clinically-relevant low concentrations (as low as 5 cells/ml), with the IMM chip showing up to 100% magnetic capture capability.

9.
Cell Chem Biol ; 26(3): 366-377.e12, 2019 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-30661989

RESUMEN

Peroxiredoxin 1 (Prx1) and glutaredoxin 3 (Grx3) are two major antioxidant proteins that play a critical role in maintaining redox homeostasis for tumor progression. Here, we identify the prototypical pyranonaphthoquinone natural product frenolicin B (FB) as a selective inhibitor of Prx1 and Grx3 through covalent modification of active-site cysteines. FB-targeted inhibition of Prx1 and Grx3 results in a decrease in cellular glutathione levels, an increase of reactive oxygen species (ROS), and concomitant inhibition of cancer cell growth, largely by activating the peroxisome-bound tuberous sclerosis complex to inhibit mTORC1/4E-BP1 signaling axis. FB structure-activity relationship studies reveal a positive correlation between inhibition of 4E-BP1 phosphorylation, ROS-mediated cancer cell cytotoxicity, and suppression of tumor growth in vivo. These findings establish FB as the most potent Prx1/Grx3 inhibitor reported to date and also notably highlight 4E-BP1 phosphorylation status as a potential predictive marker in response to ROS-based therapies in cancer.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Antineoplásicos/química , Proteínas de Ciclo Celular/metabolismo , Glutarredoxinas/metabolismo , Peroxirredoxinas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Glutarredoxinas/antagonistas & inhibidores , Humanos , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratones , Ratones Desnudos , Naftoquinonas/química , Naftoquinonas/farmacología , Naftoquinonas/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Peroxirredoxinas/antagonistas & inhibidores , Fosforilación/efectos de los fármacos , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Transducción de Señal/efectos de los fármacos , Trasplante Heterólogo
10.
Bioinformatics ; 35(15): 2626-2633, 2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-30590394

RESUMEN

MOTIVATION: Protein post-translational modifications (PTMs) regulate a wide range of cellular protein functions. Many PTM sites from the same (intra) or different (inter) proteins often cooperate with each other to perform a function, which is defined as PTM cross-talk. PTM cross-talk within proteins attracted great attentions in the past a few years. However, the inter-protein PTM cross-talk is largely under studied due to its large protein pair space and lack of a gold standard dataset, even though the PTM interplay between proteins is a key element in cell signaling and regulatory networks. RESULTS: In this study, 199 inter-protein PTM cross-talk pairs in 82 pairs of human proteins were collected from literature, which to our knowledge is the first effort in compiling such dataset. By comparing with background PTM pairs from the same protein pairs, we found that inter-protein cross-talk PTM pairs have higher sequence co-evolution at both PTM residue and motif levels. Also, we found that cross-talk PTMs have higher co-modification across multiple species and 88 human tissues or conditions. Furthermore, we showed that these features are predictive for PTM cross-talk between proteins, and applied a random forest model to integrate these features with achieving an area under the receiver operating characteristic curve of 0.81 in 10-fold cross-validation, prevailing over using any single feature alone. Therefore, this method would be a valuable tool to identify inter-protein PTM cross-talk at proteome-wide scale. AVAILABILITY AND IMPLEMENTATION: A web server for prioritization of both intra- and inter-protein PTM cross-talk candidates is at http://bioinfo.bjmu.edu.cn/ptm-x/. Python code for local computer is also freely available at https://github.com/huangyh09/PTM-X. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Procesamiento Proteico-Postraduccional , Fenómenos Fisiológicos Celulares , Humanos , Proteoma , Curva ROC
11.
Nat Commun ; 8(1): 2207, 2017 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-29263324

RESUMEN

Loss of 4E-BP1 expression has been linked to cancer progression and resistance to mTOR inhibitors, but the mechanism underlying 4E-BP1 downregulation in tumors remains unclear. Here we identify Snail as a strong transcriptional repressor of 4E-BP1. We find that 4E-BP1 expression inversely correlates with Snail level in cancer cell lines and clinical specimens. Snail binds to three E-boxes present in the human 4E-BP1 promoter to repress transcription of 4E-BP1. Ectopic expression of Snail in cancer cell lines lacking Snail profoundly represses 4E-BP1 expression, promotes cap-dependent translation in polysomes, and reduces the anti-proliferative effect of mTOR kinase inhibitors. Conversely, genetic and pharmacological inhibition of Snail function restores 4E-BP1 expression and sensitizes cancer cells to mTOR kinase inhibitors by enhancing 4E-BP1-mediated translation-repressive effect on cell proliferation and tumor growth. Our study reveals a critical Snail-4E-BP1 signaling axis in tumorigenesis, and provides a rationale for targeting Snail to improve mTOR-targeted therapies.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Fosfoproteínas/genética , Inhibidores de Proteínas Quinasas/farmacología , Factores de Transcripción de la Familia Snail/genética , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Células A549 , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Proteínas de Ciclo Celular , Línea Celular , Línea Celular Tumoral , Perros , Células HCT116 , Humanos , Células MCF-7 , Células de Riñón Canino Madin Darby , Masculino , Ratones , Ratones Desnudos , Células 3T3 NIH , Neoplasias/genética , Neoplasias/metabolismo , Fosfoproteínas/metabolismo , Factores de Transcripción de la Familia Snail/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
12.
Oncotarget ; 8(26): 42438-42454, 2017 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-28465491

RESUMEN

Genomic alterations involving translocations of the ETS-related gene ERG occur in approximately half of prostate cancer cases. These alterations result in aberrant, androgen-regulated production of ERG protein variants that directly contribute to disease development and progression. This study describes the discovery and characterization of a new class of small molecule ERG antagonists identified through rational in silico methods. These antagonists are designed to sterically block DNA binding by the ETS domain of ERG and thereby disrupt transcriptional activity. We confirmed the direct binding of a lead compound, VPC-18005, with the ERG-ETS domain using biophysical approaches. We then demonstrated VPC-18005 reduced migration and invasion rates of ERG expressing prostate cancer cells, and reduced metastasis in a zebrafish xenograft model. These results demonstrate proof-of-principal that small molecule targeting of the ERG-ETS domain can suppress transcriptional activity and reverse transformed characteristics of prostate cancers aberrantly expressing ERG. Clinical advancement of the developed small molecule inhibitors may provide new therapeutic agents for use as alternatives to, or in combination with, current therapies for men with ERG-expressing metastatic castration-resistant prostate cancer.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Descubrimiento de Drogas , Motivo ETS , Neoplasias de la Próstata/metabolismo , Dominios y Motivos de Interacción de Proteínas , Regulador Transcripcional ERG/química , Regulador Transcripcional ERG/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Descubrimiento de Drogas/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Modelos Moleculares , Conformación Molecular , Proteínas de Fusión Oncogénica/química , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Unión Proteica , Relación Estructura-Actividad , Regulador Transcripcional ERG/genética , Pez Cebra
14.
Sci Rep ; 6: 28600, 2016 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-27339395

RESUMEN

The improvement and implementation of a colonoscopy technique has led to increased detection of laterally spreading tumors (LSTs), which are presumed to constitute an aggressive type of colonic neoplasm. Early diagnosis and treatment of LSTs is clinically challenging. To overcome this problem, we employed iTRAQ to identify LST-specific protein biomarkers potentially involved in LST progression. In this study, we identified 2,001 differentially expressed proteins in LSTs using iTRAQ-based proteomics technology. Lipocalin-2 (LCN-2) was the most up-regulated protein. LSTs expression levels of LCN-2 and matrix metallopeptidase-9 (MMP-9) showed positive correlation with worse pathological grading, and up-regulation of these proteins in LSTs was also reflected in serum. Furthermore, LCN-2 protein overexpression was positively correlated with MMP-9 protein up-regulation in the tumor tissue and serum of LST patients (former rs = 0.631, P = 0.000; latter rs = 0.815, P = 0.000). Our results suggest that LCN-2 constitutes a potential biomarker for LST disease progression and might be a novel therapeutic target in LSTs.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Colon/metabolismo , Neoplasias del Colon/metabolismo , Lipocalina 2/metabolismo , Adulto , Colon/patología , Neoplasias del Colon/patología , Colonoscopía/métodos , Femenino , Humanos , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Proteómica/métodos , Regulación hacia Arriba/fisiología
15.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(5): 655-9, 2016 May.
Artículo en Chino | MEDLINE | ID: mdl-27222180

RESUMEN

OBJECTIVE: To evaluate the effect of palmitic acid (PA) on oxidative stress and activation of inflammasomes in hepatocytes. METHODS: To test the dose-dependent effect of PA on normal murine hepatocytes AML12, the cells were treated with 0, 0.15, 0.25 and 0.4 mmol/L of palmitic acid (PA). The cells were also divided into blank control group, 0.25 mmol/L PA group and 0.25 mmol/L PA+N-acetylcysteine (NAC) group to examine the effect of reactive oxygen species (ROS) on the activation of inflammasomes. After 24 h of treatment, lipid accumulation, total ROS, mitochondrial ROS, expression and localization of NOX4, and expressions of inflammasomes and IL-1ß were detected in the hepatocytes. RESULTS: Compared with the control cells, PA treatment of the cells significantly increased cytoplasmic lipid accumulation, concentrations of total ROS (12 463.09±2.72 vs 6691.23±2.45, P=0.00) and mitochondrial ROS (64.98±0.94 vs 45.04±0.92, P=0.00), and the expressions of NOX4, NLRP3, ASC, caspase-1, and IL-1ß (1603.52±1.32 vs 2629.33±2.57, P=0.00). The mitochondria and NOX4 were found to be co-localized in the cytoplasm. NAC obviously reduced cellular ROS level stimulated by PA (7782.15±2.87 vs 5445.6±1.17, P=0.00) and suppressed the expressions of NLRP3, ASC and caspase-1. CONCLUSION: PA treatment can stimulate lipid accumulation in hepatocytes and induce oxidative stress through NOX4 and mitochondria pathway to activate inflammasomes and stimulate the secretion of IL-1ß.


Asunto(s)
Hepatocitos/efectos de los fármacos , Inflamasomas/efectos de los fármacos , Estrés Oxidativo , Ácido Palmítico/farmacología , Acetilcisteína/farmacología , Animales , Proteínas Portadoras/metabolismo , Caspasa 1/metabolismo , Células Cultivadas , Hepatocitos/metabolismo , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Ratones , Mitocondrias/efectos de los fármacos , NADPH Oxidasa 4 , NADPH Oxidasas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR , Especies Reactivas de Oxígeno/metabolismo
16.
Technol Health Care ; 23 Suppl 1: S161-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26410321

RESUMEN

BACKGROUND: The intrinsic mechanism of multimorbidity is difficult to recognize and prediction and diagnosis are difficult to carry out accordingly. Bayesian networks can help to diagnose multimorbidity in health care, but it is difficult to obtain the conditional probability table (CPT) because of the lack of clinically statistical data. OBJECTIVE: Today, expert knowledge and experience are increasingly used in training Bayesian networks in order to help predict or diagnose diseases, but the CPT in Bayesian networks is usually irrational or ineffective for ignoring realistic constraints especially in multimorbidity. METHODS: In order to solve these problems, an evidence reasoning (ER) approach is employed to extract and fuse inference data from experts using a belief distribution and recursive ER algorithm, based on which evidence reasoning method for constructing conditional probability tables in Bayesian network of multimorbidity is presented step by step. RESULTS: A multimorbidity numerical example is used to demonstrate the method and prove its feasibility and application. Bayesian network can be determined as long as the inference assessment is inferred by each expert according to his/her knowledge or experience. CONCLUSIONS: Our method is more effective than existing methods for extracting expert inference data accurately and is fused effectively for constructing CPTs in a Bayesian network of multimorbidity.


Asunto(s)
Teorema de Bayes , Comorbilidad , Sistemas Especialistas , Probabilidad , Algoritmos , Humanos
17.
Int J Colorectal Dis ; 30(3): 375-80, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25596026

RESUMEN

OBJECTIVE: Small rectal carcinoid tumors (<10 mm) are often removed via endoscopic submucosal dissection (ESD). However, the use of ESD for tumors of an intermediate size (7-16 mm) is less well documented. This study aimed to evaluate the efficacy and safety of ESD compared with endoscopic mucosal resection using a cap (EMR-C) for the treatment of 7-16-mm rectal carcinoids. MATERIAL AND METHODS: From September 2007 to August 2012, 55 patients with large rectal carcinoid tumors were treated by EMR-C (30 cases) or ESD (25 cases). The en bloc resection rate, pathological complete response (pCR) rate, procedure time, and incidence rates of complications, local recurrence, and distant metastasis were evaluated. RESULTS: The basic and clinical characteristics of the patients in the two groups did not differ significantly (p > 0.05). The mean procedure time was longer for ESD than EMR-C (24.79 ± 4.89 vs. 9.52 ± 2.14 min, p < 0.001). The rates of en bloc resection and pCR were higher with ESD than with EMR-C (100 vs. 83.33 %, and 100 vs. 70.00 %, respectively). No patients in the EMR-C group experienced complications. However, in the ESD group, two cases of perforation occurred, and one patient experienced delayed bleeding. These complications were successfully managed via endoscopical therapy. Five cases of local recurrence were detected after EMR-C, whereas no patients experienced recurrence after ESD. CONCLUSIONS: Compared with EMR-C, ESD appears to be a more favorable therapeutic option for the treatment of rectal carcinoid tumors less than 16 mm in diameter based on improved rates of pCR and local recurrence.


Asunto(s)
Tumor Carcinoide/cirugía , Disección/métodos , Mucosa Intestinal/cirugía , Neoplasias Intestinales/cirugía , Proctoscopía/métodos , Neoplasias del Recto/cirugía , Adulto , Tumor Carcinoide/patología , Femenino , Humanos , Neoplasias Intestinales/patología , Masculino , Persona de Mediana Edad , Neoplasias del Recto/patología , Resultado del Tratamiento
18.
Gut Liver ; 9(5): 649-56, 2015 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-25266811

RESUMEN

BACKGROUND/AIMS: Recent papers have highlighted the role of diet and lifestyle habits in irritable bowel syndrome (IBS), but very few population-based studies have evaluated this association in developing countries. The aim of this study was to evaluate the association between diet and lifestyle habits and IBS. METHODS: A food frequency and lifestyle habits questionnaire was used to record the diet and lifestyle habits of 78 IBS subjects and 79 healthy subjects. Cross-tabulation analysis and logistic regression were used to reveal any association among lifestyle habits, eating habits, food consumption frequency, and other associated conditions. RESULTS: The results from logistic regression analysis indicated that IBS was associated with irregular eating (odds ratio [OR], 3.257), physical inactivity (OR, 3.588), and good quality sleep (OR, 0.132). IBS subjects ate fruit (OR, 3.082) vegetables (OR, 3.778), and legumes (OR, 2.111) and drank tea (OR, 2.221) significantly more frequently than the control subjects. After adjusting for age and sex, irregular eating (OR, 3.963), physical inactivity (OR, 6.297), eating vegetables (OR, 7.904), legumes (OR, 2.674), drinking tea (OR, 3.421) and good quality sleep (OR, 0.054) were independent predictors of IBS. CONCLUSIONS: This study reveals a possible association between diet and lifestyle habits and IBS.


Asunto(s)
Dieta/efectos adversos , Conducta Alimentaria , Síndrome del Colon Irritable/etiología , Estilo de Vida , Adulto , Estudios de Casos y Controles , China , Femenino , Voluntarios Sanos , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios
20.
Carcinogenesis ; 33(12): 2558-67, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23027626

RESUMEN

Approximately half of prostate cancers (PCa) carry TMPRSS2-ERG translocations; however, the clinical impact of this genomic alteration remains enigmatic. Expression of v-ets erythroblastosis virus E26 oncogene like (avian) gene (ERG) promotes prostatic epithelial dysplasia in transgenic mice and acquisition of epithelial-to-mesenchymal transition (EMT) characteristics in human prostatic epithelial cells (PrECs). To explore whether ERG-induced EMT in PrECs was associated with therapeutically targetable transformation characteristics, we established stable populations of BPH-1, PNT1B and RWPE-1 immortalized human PrEC lines that constitutively express flag-tagged ERG3 (fERG). All fERG-expressing populations exhibited characteristics of in vitro and in vivo transformation. Microarray analysis revealed >2000 commonly dysregulated genes in the fERG-PrEC lines. Functional analysis revealed evidence that fERG cells underwent EMT and acquired invasive characteristics. The fERG-induced EMT transcript signature was exemplified by suppressed expression of E-cadherin and keratins 5, 8, 14 and 18; elevated expression of N-cadherin, N-cadherin 2 and vimentin, and of the EMT transcriptional regulators Snail, Zeb1 and Zeb2, and lymphoid enhancer-binding factor-1 (LEF-1). In BPH-1 and RWPE-1-fERG cells, fERG expression is correlated with increased expression of integrin-linked kinase (ILK) and its downstream effectors Snail and LEF-1. Interfering RNA suppression of ERG decreased expression of ILK, Snail and LEF-1, whereas small interfering RNA suppression of ILK did not alter fERG expression. Interfering RNA suppression of ERG or ILK impaired fERG-PrEC Matrigel invasion. Treating fERG-BPH-1 cells with the small molecule ILK inhibitor, QLT-0267, resulted in dose-dependent suppression of Snail and LEF-1 expression, Matrigel invasion and reversion of anchorage-independent growth. These results suggest that ILK is a therapeutically targetable mediator of ERG-induced EMT and transformation in PCa.


Asunto(s)
Neoplasias de la Próstata/patología , Proteínas Serina-Treonina Quinasas/fisiología , Transactivadores/fisiología , Animales , Compuestos Azo/farmacología , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Humanos , Factor de Unión 1 al Potenciador Linfoide/fisiología , Masculino , Ratones , Invasividad Neoplásica , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Pirazoles/farmacología , Factores de Transcripción de la Familia Snail , Factores de Transcripción/fisiología , Regulador Transcripcional ERG
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