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OBJECTIVE: To develop and validate a deep learning (DL) model based on CT for differentiating bone islands and osteoblastic bone metastases. MATERIALS AND METHODS: The patients with sclerosing bone lesions (SBLs) were retrospectively included in three hospitals. The images from site 1 were randomly assigned to the training (70%) and intrinsic verification (10%) datasets for developing the two-dimensional (2D) DL model (single-slice input) and "2.5-dimensional" (2.5D) DL model (three-slice input) and to the internal validation dataset (20%) for evaluating the performance of both models. The diagnostic performance was evaluated using the internal validation set from site 1 and additional external validation datasets from site 2 and site 3. And statistically analyze the performance of 2D and 2.5D DL models. RESULTS: In total, 1918 SBLs in 728 patients in site 1, 122 SBLs in 71 patients in site 2, and 71 SBLs in 47 patients in site 3 were used to develop and test the 2D and 2.5D DL models. The best performance was obtained using the 2.5D DL model, which achieved an AUC of 0.996 (95% confidence interval [CI], 0.995-0.996), 0.958 (95% CI, 0.958-0.960), and 0.952 (95% CI, 0.951-0.953) and accuracies of 0.950, 0.902, and 0.863 for the internal validation set, the external validation set from site 2 and site 3, respectively. CONCLUSION: A DL model based on a three-slice CT image input (2.5D DL model) can improve the prediction of osteoblastic bone metastases, which can facilitate clinical decision-making. KEY POINTS: ⢠This study investigated the value of deep learning models in identifying bone islands and osteoblastic bone metastases. ⢠Three-slice CT image input (2.5D DL model) outweighed the 2D model in the classification of sclerosing bone lesions. ⢠The 2.5D deep learning model showed excellent performance using the internal (AUC, 0.996) and two external (AUC, 0.958; AUC, 0.952) validation sets.
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Neoplasias Óseas , Aprendizaje Profundo , Artropatías , Humanos , Neoplasias Óseas/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
The high-grade C2+ products from CO2 photoreduction are limited by the kinetic bottleneck. Herein, a multifunctional Au/hydroxide interface was put forward to improve the C-C coupling. As a prototype, the synthesized Au/ZnSn(OH)6 tuned the CO generation and afforded about 50% electrons toward C2H6 selectivity. The prominent enhancement resulted from the following effects: (1) strong metal-support electronic interactions built an electric field at the interface of ZnSn(OH)6 nearby the Au nanoparticles, leading to fast transfer of electrons for the C-H and C-C bonding reactions. (2) The surface solid-state Sn-OH and Zn-OH lattice hydroxyls served as donors to feed rich H+ and oxygen vacancies (OVs) via hole-induced oxidation for the boosted C2H6 formation. (3) The synergetic OVs and Au sites allowed efficient e-/H+ to boost *CO hydrogenation toward *CH3 and *CH3*CH3 formation into the C2H6 product.
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BACKGROUND: To determine the related imaging findings and risk factors to refracture of the cemented vertebrae after percutaneous vertebroplasty (PVP) treatment. METHODS: Patients who were treated with PVP for single vertebral compression fractures (VCFs) and met this study's inclusion criteria were retrospectively reviewed from January 2012 to January 2019. The follow-up period was at least 2 years. Forty-eight patients with refracture of the cemented vertebrae and 45 non-refractured patients were included. The following variates were reviewed: age, sex, fracture location, bone mineral density (BMD), intravertebral cleft (IVC), kyphotic angle (KA), wedge angle, endplate cortical disruption, cement volume, surgical approach, non-PMMA-endplate-contact (NPEC), cement leakage, other vertebral fractures, reduction rate (RR), and reduction angle (RA). Multiple logistic regression modeling was used to identify the independent risk factors of refracture. RESULTS: Refracture was found in 48 (51.6%) patients. Four risk factors, including IVC (P = 0.005), endplate cortical disruption (P = 0.037), larger RR (P = 0.007), and NPEC (P = 0.006) were found to be significant independent risk factors for refracture. CONCLUSIONS: Patients with IVC or larger RR, NPEC, or endplate cortical disruption have a high risk of refracture in the cemented vertebrae after PVP.
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Fracturas por Compresión , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Vertebroplastia , Cementos para Huesos/efectos adversos , Fracturas por Compresión/diagnóstico por imagen , Fracturas por Compresión/epidemiología , Fracturas por Compresión/cirugía , Humanos , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/cirugía , Estudios Retrospectivos , Factores de Riesgo , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/cirugía , Columna Vertebral , Resultado del Tratamiento , Vertebroplastia/efectos adversosRESUMEN
BACKGROUND: Although whole-lesion apparent diffusion coefficient (ADC) histogram has been increasingly used for breast lesions, it has not been routinely used in clinical practice as an emergent promising imaging tool. PURPOSE: To evaluate the performance of whole-lesion ADC histogram analysis metrics for differentiating benign and malignant breast lesions. MATERIAL AND METHODS: A systematic PubMed/EMBASE/Cochrane electronic database search was performed for original diagnostic studies from 1 January 1970 to 2 January 2019. Summary estimates of diagnostic accuracy were generated and meta-regression was performed to explore sources of heterogeneity according to study and magnetic resonance imaging characteristics. RESULTS: Five original articles involving 493 patients were included in the meta-analysis. The pooled sensitivity and specificity of whole-lesion ADC histogram analysis were 0.85 (95% confidence interval [CI] = 0.81-0.89) and 0.79 (95% CI = 0.72-0.84) for distinguishing benign and malignant breast lesions, respectively. The area under the curve (AUC) was 0.9178. No publication bias was detected (P = 0.51). In subgroup analysis, the summary sensitivity and specificity of 50th percentile ADC value were 0.81 (95% CI = 0.71-0.88) and 0.86 (95% CI = 0.74-0.94), respectively. Meta-regression analysis indicated no covariates were sources of heterogeneity (P > 0.05). CONCLUSION: Whole-lesion ADC histogram analysis demonstrated good diagnostic performance for differentiating between benign and malignant breast lesions, with 50th percentile ADC value showing higher diagnostic accuracy than other histogram parameters. Given the limited number of studies included in the analysis, the findings from our meta-analysis will need further confirmation in future research.
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Neoplasias de la Mama/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias de la Mama/patología , Diagnóstico Diferencial , Femenino , HumanosRESUMEN
Gliomas are highly malignant tumors, the most common of which are astrocytomas. A growing number of studies suggest that dysregulation of miRNAs is a frequent event contributing to the pathogenesis of gliomas. In this study, we found that over-expression of miR-132 inhibited cell proliferation and migration and triggered apoptosis, while knockdown of miR-132 showed opposite effects. PEA-15 was identified as a direct target of miR-132. Reintroduction of PEA-15 without 3'UTR region reversed the inhibitory effects of miR-132 on cell proliferation, migration, and apoptosis. MiR-132 was inversely correlated with the PEA-15 expression. CREB (cAMP response element binding protein) and KLF (Krüppel-like factor 8) were conformed as transcription factors of miR-132, which bidirectionally regulate the expression of miR-132. Our study suggests that miR-132 is an important tumor suppressor of astrocytoma progression by targeting PEA-15, while CREB and KLF can modulate the expression of miR-132, thus providing new insight into the molecular mechanisms underlying astrocytoma progression in vitro.
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Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Regulación Neoplásica de la Expresión Génica/fisiología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , MicroARNs/metabolismo , Fosfoproteínas/metabolismo , Análisis de Varianza , Apoptosis/genética , Apoptosis/fisiología , Proteínas Reguladoras de la Apoptosis , Astrocitoma/patología , Neoplasias Encefálicas/patología , Proteína de Unión a CREB/genética , Proteína de Unión a CREB/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Movimiento Celular/fisiología , Proliferación Celular/genética , Proliferación Celular/fisiología , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica/genética , Glioma , Células HEK293 , Humanos , Factores de Transcripción de Tipo Kruppel , MicroARNs/genética , ARN Mensajero , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Sincalida/metabolismo , Factores de Tiempo , TransfecciónRESUMEN
The construction of two-dimensional (2D) van der Waals (vdW) heterostructures over black phosphorus (BP) has been attracting significant attention to better utilize its inherent properties. The sandwich of zero-dimensional (0D) noble metals within BP-based vdW heterostructures can provide efficient catalytic channels, modulating their surface redox potentials and therefore inducing versatile functionalities. Herein, we realize a 2D WS2-Au-BP heterostructure, in which Au nanoparticles are connected between BP and WS2 via ionic bonds. The ultralow conduction band minimum position, the reduced adsorption energies of O2, and the increased dissociation barrier energy of O2- into 2O contribute greatly to improving the long-term stability of BP in the air. The formation of heterostructures can reduce the potential barrier energy in target gas molecules, thus enhancing the absorption energy and charge transfer. Taking the paramagnetic NO2 gas molecules as a representative, a stable response magnitude of 2.11 to 100 ppb NO2 is achieved for 80 days, which is far larger than the initial responses of most BP-based materials. A practical gas sensing system is also developed to demonstrate its real-world implementation. This work provides a promising demonstration of 0D noble metal within 2D BP-based vdW heterostructure for simultaneously improving the long-term stability and room-temperature reversible gas sensing.
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BACKGROUND: Deep vein thrombosis (DVT) is prone to occur in the recovery of critically ill neurosurgical patients, increasing economic and psychological pressure, and even endangering life. Plan-Do-Check-Action (PDCA) cycle is a kind of quality management cycle procedure, which can help DVT treatment correctly understand the cause of disease and take effective preventive and nursing measures. The air wave pressure therapy instrument takes pressure therapy as the core, forming circulating pressure on limbs and tissues, promoting the flow of blood and lymph, improving the effect of microcirculation, accelerating the return of limb tissue fluid, and preventing thrombosis and limb edema. METHODS: A total of 98 critical neurosurgery patients were selected as the study subjects. On the basis of PDCA circulation treatment, the patients were treated with air pressure wave for 30 minutes/time, twice/day and 14 days. Before and after treatment, the indexes of coagulation function, hemorheology (plasma viscosity, whole blood high shear viscosity and whole blood low shear viscosity), lower limb circumference (15 cm above and below the patella) and Barthel index (BI) scores were observed and recorded. DVT was observed by vascular Doppler ultrasound before and after treatment, and the incidence was calculated. RESULTS: The prothrombin time (18.09 s) and thrombin time (17.66 s) after treatment were higher than those before treatment (12.98 s, 130.7 s), and fibrinogen decreased (4.21 vs. 3.31 g/L). The hemorheological indexes of the patients after treatment were plasma viscosity (1.49 mPa/s, 10.8 mPa/s), whole blood high shear viscosity (6.34 mPa/s, 4.47 mPa/s), whole blood low shear viscosity (9.89 mPa/s, 6.32 mPa/s), circumference at 15 cm below the patella (52.29 cm, 45.23 cm), and circumference at 15 cm above the patella (36.17 cm, 31.38 cm). The BI score showed that the number of patients with severe dependence on grade A (46/15) and moderate dependence on grade B (50/14) decreased after treatment, and the average BI score of patients with combined treatment increased (43.87 and 79.86). After treatment, the number of patients with DVT (20/4) and the incidence of DVT (20.40816327%, 4.081632653%) decreased significantly (P<0.05). CONCLUSIONS: PDCA circulation combined with barometric wave therapy can significantly improve DVT in critical neurosurgical patients.
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RATIONALE AND OBJECTIVES: Lymphovascular invasion (LVI) plays an important role in the prediction of metastasis and prognosis in breast cancer (BC) patients. The present study assessed correlations between preoperative breast MRI, clinical features, and LVI in patients with invasive ductal carcinoma (IDC) and identified risk factors based on these correlation factors. MATERIALS AND METHODS: Patients confirmed with IDC between 01/2012 and 12/2021 were retrospectively reviewed at our hospital. A total of 5 clinical and 14 MRI features to characterize tumours were extracted. LVI evaluated in hematoxylin and eosin sections. T-test and chi-square tests were used to compare the differences in clinical and MRI features between the LVI positive and negative groups. The associations between individual features and LVI were analysed by univariable logistic regression analysis, and risk factors for LVI were identified by multivariable logistic regression analysis based on these correlation factors. RESULTS: This study included 353 patients with IDC, including 130 with positive LVI. Age, CEA, CA-153, amount of fibroglandular tissue (FGT), background parenchymal enhancement, tumour size, shape, skin thickening, nipple retraction, adjacent vessel sign, and axillary lymph node (ALN) size in the LVI positive group were significantly different from the LVI negative group (all p<0.05). Multivariate logistic regression analysis revealed that age (odds ratio OR = 1.030), CA-153 (OR = 1.018), heterogeneous FGT (OR = 2.484), shape (OR = 2.157), and ALN size (OR = 1.051) were risk factors for LVI (all p<0.05). CONCLUSION: Preoperative breast MRI and clinical features correlated with LVI, age, CA-153, heterogeneous FGT, shape, and ALN size are risk factors for LVI in patients with IDC.
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Carcinoma Ductal , Imagen por Resonancia Magnética , Humanos , Estudios Retrospectivos , Metástasis Linfática , Factores de RiesgoRESUMEN
Phosphorene nanoribbons (PNRs) combine the flexibility of one-dimensional (1D) nanomaterials with the large specific surface area and the edge and electron confinement effects of two-dimensional (2D) nanomaterials. In spite of the substantial advances in bulk black phosphorus (BP) manufacturing, achieving PNRs without degradation is still a big challenge. In this work, we present a strategy for the space-confined chemical vapor transport synthesis of quasi-one-dimensional surface-passivated monocrystalline PNRs on a silicon substrate. The growth mechanism of the PNRs is proposed by combining experimental results and DFT calculations, indicating that the P4 molecules can break, restructure, and epitaxially nucleate on the surface of the Au3SnP7 catalyst, and finally prefer to grow along the zigzag (ZZ) direction to form PNRs. The low gas flow rate and an appropriate phosphorus molecule concentration allow the growth of PNRs with structural integrity, which can be regulated by the amount of red phosphorus and the confined space.
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Realizing efficient detection of ultra-low concentrations of hazardous gases contributes to air pollution monitoring, ecosystem and human health protection. Herein, we firstly fabricated the nanoflower-like WO3/WS2 composites by a facile process to highly sensitively detect NO2 at room temperature. The WO3 content in the WO3/WS2 composites can be adjusted by altering the calcination temperature, and the WO3 nanoparticles disperse uniformly on the WS2 surface, forming the WO3/WS2 heterojunction. The room-temperature responses of WO3/WS2 composites gradually climb with the NO2 concentration increasing from 0.005 to 5 ppm, and the WW-280 and WW-300 composites possess the optimal gas sensitivity when the NO2 concentrations are lower and higher than 100 ppb, respectively. In particular, the two WO3/WS2 composites present the limitation of detection (LOD) of ≤ 5 ppb, and they exhibit the excellent selectivity, good reproducibility and long-term stability towards NO2. A possible gas sensing mechanism was also proposed from the point of views of gas adsorption, redox reactions and electron transfer. The appropriate WO3 content and molar ratio of hexagonal to monoclinic WO3, and the formation of WO3/WS2 p-n heterojunction can contribute to the high sensitivity of WO3/WS2 composite to various concentrations of NO2. This work offers a promising gas sensing material for room-temperature detection to low concentrations of NO2.
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Ecosistema , Dióxido de Nitrógeno , Humanos , Temperatura , Reproducibilidad de los Resultados , GasesRESUMEN
Objective: To develop and validate an artificial intelligence diagnostic system based on X-ray imaging data for diagnosing vertebral compression fractures (VCFs). Methods: In total, 1904 patients who underwent X-ray at four independent hospitals were retrospectively (n=1847) and prospectively (n=57) enrolled. The participants were separated into a development cohort, a prospective test cohort and three external test cohorts. The proposed model used a transfer learning method based on the ResNet-18 architecture. The diagnostic performance of the model was evaluated using receiver operating characteristic curve (ROC) analysis and validated using a prospective validation set and three external sets. The performance of the model was compared with three degrees of musculoskeletal expertise: expert, competent, and trainee. Results: The diagnostic accuracy for identifying compression fractures was 0.850 in the testing set, 0.829 in the prospective set, and ranged from 0.757 to 0.832 in the three external validation sets. In the human and deep learning (DL) collaboration dataset, the area under the ROC curves(AUCs) in acute, chronic, and pathological compression fractures were as follows: 0.780, 0.809, 0.734 for the DL model; 0.573, 0.618, 0.541 for the trainee radiologist; 0.701, 0.782, 0.665 for the competent radiologist; 0.707,0.732, 0.667 for the expert radiologist; 0.722, 0.744, 0.610 for the DL and trainee; 0.767, 0.779, 0.729 for the DL and competent; 0.801, 0.825, 0.751 for the DL and expert radiologist. Conclusions: Our study offers a high-accuracy multi-class deep learning model which could assist community-based hospitals in improving the diagnostic accuracy of VCFs.
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Enfermedades Óseas Metabólicas , Aprendizaje Profundo , Fracturas por Compresión , Fracturas de la Columna Vertebral , Humanos , Inteligencia Artificial , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas por Compresión/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
PURPOSE: We developed and validated a CT-based radiomics nomogram to predict HER2 status in patients with adenocarcinoma of esophagogastric junction (AEG). METHOD: A total of 101 patients with HER2-positive (n=46) and HER2-negative (n=55) esophagogastric junction adenocarcinoma (AEG) were retrospectively analyzed. They were then randomly divided into a training cohort (n=70) and a verification cohort (n=31). The radiomics features were obtained from the portal phase of the CT enhanced scan. We used the least absolute shrinkage and selection operator (LASSO) logistic regression method to select the best radiomics features in the training cohort, combined them linearly, and used the radiomics signature formula to calculate the radiomics score (Rad-score) of each AEG patient. A multivariable logistic regression method was applied to develop a prediction model that incorporated the radiomics signature and independent risk predictors. The prediction performance of the nomogram was evaluated using the training and validation cohorts. RESULT: In the training (P<0.001) and verification groups (P<0.001), the radiomics signature combined with seven radiomics features was significantly correlated with HER2 status. The nomogram composed of CT-reported T stage and radiomics signature showed very good predictive performance for HER2 status. The area under the curve (AUC) of the training cohort was 0.946 (95% CI: 0.919-0.973), and that of the validation group was 0.903 (95% CI: 0.847-0.959). The calibration curve of the radiomics nomogram showed a good degree of calibration. Decision-curve analysis revealed that the radiomics nomogram was useful. CONCLUSION: The nomogram CT-based radiomics signature combined with CT-reported T stage can better predict the HER2 status of AEG before surgery. It can be used as a non-invasive prediction tool for HER2 status and is expected to guide clinical treatment decisions in clinical practice, and it can assist in the formulation of individualized treatment plans.
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OBJECTIVES: To assess the diagnostic accuracy of diffusion-weighted imaging (DWI) in predicting the malignant potential in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: A systematic search of articles investigating the diagnostic performance of DWI for prediction of malignant potential in IPMNs was conducted from PubMed, Embase, and Web of Science from January 1997 to 10 February 2020. QUADAS-2 tool was used to evaluate the study quality. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and their 95% confidence intervals (CIs) were calculated. The summary receiver operating characteristic (SROC) curve was then plotted, and meta-regression was also performed to explore the heterogeneity. RESULTS: Five articles with 307 patients were included. The pooled sensitivity and specificity of DWI were 0.74 (95% CI: 0.65, 0.82) and 0.94 (95% CI: 0.78, 0.99), in evaluating the malignant potential of IPMNs. The PLR was 13.5 (95% CI: 3.1, 58.7), the NLR was 0.27 (95% CI: 0.20, 0.37), and DOR was 50.0 (95% CI: 11.0, 224.0). The area under the curve (AUC) of SROC curve was 0.84 (95% CI: 0.80, 0.87). The meta-regression showed that the slice thickness of DWI (p = 0.02) and DWI parameter (p= 0.01) were significant factors affecting the heterogeneity. CONCLUSIONS: DWI is an effective modality for the differential diagnosis between benign and malignant IPMNs. The slice thickness of DWI and DWI parameter were the main factors influencing diagnostic specificity.
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BACKGROUND: Atypical meningiomas (AM) are WHO grade II tumors with high heterogeneity and invasiveness, which are unique in their clinical presentation, imaging, pathology, treatment, and prognosis. In 2016, the diagnosis of AM remodified by the classification of central nervous system tumors of World Health Organization (WHO). In order to further analyze the diagnosis and treatment characteristics of AM, the clinical diagnosis, surgery treatment and follow-up data of 6 patients with AM in our hospital from January 2016 to December 2019 were analyzed retrospectively. METHODS: The clinical diagnosis, treatment and follow-up data of six patients with AM admitted to our hospital between January 2016 and December 2019 were analyzed retrospectively, and related literature was reviewed. RESULTS: The main clinical symptoms of the patients were increased intracranial pressure and functional area symptoms. MRI showed obvious enhancement, an unclear boundary with adjacent brain tissue, a large edema signal shadow in the white matter of peripheral brain tissue, and rapid enlargement in some cases. Pathological manifestations showed local necrosis and increased nuclear division activity. The results of immunocytochemistry showed that vimentin and epithelial membrane antigen (EMA) were positive, S-100 protein (S-100) and glial fibrillary acidic protein (GFAP) were negative, and the Ki-67 proliferation index was increased. Simpson's grade I-II resection was performed in five cases and no recurrence found after 4 to 46 months of follow-up. Simpson's grade IV resection was performed in one case and no follow-up was performed after discharge. CONCLUSIONS: AMs are highly heterogeneous and invasive. Histologic diagnosis is the gold standard for diagnosis and surgical resection is the first treatment choice. Total resection (Simpson I-II) helps to reduce recurrence.
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Rationale: Peritoneal metastasis predicts poor prognosis of gastric cancer (GC) patients, and the underlying mechanisms are poorly understood. Methods: The 2-DIGE, MALDI-TOF/TOF MS and single-cell transcriptome were used to detect differentially expressed proteins among normal gastric mucosa, primary GC and peritoneal metastatic tissues. Lentiviruses carrying shRNA and transcription activator-like effector nuclease technology were used to knock down myosin heavy chain 9 (MYH9) expression in GC cell lines. Immunofluorescence, immune transmission electron microscopy, chromatin fractionation, co-immunoprecipitation, and assays for chromatin immunoprecipitation, dual luciferase reporter, agarose-oligonucleotide pull-down, flow cytometry and cell anoikis were performed to uncover nuclear MYH9-induced ß-catenin (CTNNB1) transcription in vitro. Nude mice and conditional transgenic mice were used to investigate the findings in vivo. Results: We observed that MYH9 was upregulated in metastatic GC tissues and was associated with a poor prognosis of GC patients. Mechanistically, we confirmed that MYH9 was mainly localized in the GC cell nuclei by four potential nuclear localization signals. Nuclear MYH9 bound to the CTNNB1 promoter through its DNA-binding domain, and interacted with myosin light chain 9, ß-actin and RNA polymerase II to promote CTNNB1 transcription, which conferred resistance to anoikis in GC cells in vitro and in vivo. Staurosporine reduced nuclear MYH9 S1943 phosphorylation to inhibit CTNNB1 transcription, Wnt/ß-catenin signaling activation and GC progression in both orthotropic xenograft GC nude mouse and transgenic GC mouse models. Conclusion: This study identified that nuclear MYH9-induced CTNNB1 expression promotes GC metastasis, which could be inhibited by staurosporine, indicating a novel therapy for GC peritoneal metastasis.
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Anoicis/genética , Neoplasias Pulmonares/genética , Cadenas Pesadas de Miosina/metabolismo , Estaurosporina/farmacología , Neoplasias Gástricas/patología , beta Catenina/genética , Animales , Anoicis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Quimioterapia Adyuvante/métodos , Femenino , Gastrectomía , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Transgénicos , Cadenas Pesadas de Miosina/genética , Fosforilación/efectos de los fármacos , Regiones Promotoras Genéticas/genética , Estaurosporina/uso terapéutico , Estómago/patología , Estómago/cirugía , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Activación Transcripcional/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacos , Vía de Señalización Wnt/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The bed nucleus of the stria terminalis (BNST), a nucleus defined as part of the extended amygdala, is involved in the expression of anxiety disorders. However, the regulatory mechanisms of BNST inhibitory activity that is involved in anxiety are unknown. Here, we showed that blocking neuregulin 1 (NRG1)-ErbB4 signaling in the BNST of mice, by either neutralizing endogenous NRG1 with ecto-Erbb4 or antagonizing the ErbB4 receptor with its specific inhibitor, produced anxiogenic responses. Interestingly, application of exogenous NRG1 into the BNST induced no anxiolytic effects, suggesting saturating activity of endogenous NRG1. While infusion of the GABAA receptor antagonist bicuculline into the BNST also led to anxiety-related behaviors, it did not worsen the anxiogenic effects produced by blocking NRG1-ErbB4 signaling, suggesting possible involvement of GABAergic neurotransmission. Further, in vitro electrophysiological recordings showed that BNST NRG1-ErbB4 signaling regulated the presynaptic GABA release. Together, these results suggest that NRG1-ErbB4 signaling in the BNST may play an important role in regulating anxiety-like behaviors.
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Ansiedad/metabolismo , Neurregulina-1/metabolismo , Receptor ErbB-4/metabolismo , Núcleos Septales/metabolismo , Animales , Bicuculina/farmacología , Fármacos del Sistema Nervioso Central/farmacología , Antagonistas de Receptores de GABA-A/farmacología , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Ratones Endogámicos C57BL , Modelos Animales , Neurregulina-1/administración & dosificación , Neurregulina-1/antagonistas & inhibidores , Terminales Presinápticos/efectos de los fármacos , Terminales Presinápticos/metabolismo , Pirimidinas/farmacología , Receptor ErbB-4/antagonistas & inhibidores , Receptores de GABA-A/metabolismo , Núcleos Septales/efectos de los fármacos , Técnicas de Cultivo de Tejidos , Ácido gamma-Aminobutírico/metabolismoRESUMEN
There are limited treatment options for cartilage defects in clinical practice because of the lack of suitable biomaterials. Here, we evaluated the effects of collagen type II sponge on the articular cartilage repairing process using a cartilage injury of a rabbit knee joint model. We showed that the home-made collagen type II sponges appeared to have a suitable pore size of 93.26 ± 38.4 µm for chondrocyte growth. MRI with H&E staining results demonstrated that the effusion absorption in the collagen type II sponge treated group was quicker than that of the control group. Moreover, sporadic cartilage signals first appeared at 6 weeks in the collagen type II sponge treated group. Safranin O staining and immunohistochemical analysis confirmed that the newly formed cartilage expresses glycosaminoglycan and type II collagen matrix. Using Sirius red polarized light staining, we showed that the newly formed cartilage-like areas from the collagen type II treated group are significantly greater than those of the control group. Taken together, our data demonstrated that the home-made collagen type II sponge is able to promote cartilage repair in the cartilage injury of a rabbit knee joint model.
Asunto(s)
Cartílago Articular/lesiones , Colágeno Tipo II/uso terapéutico , Articulación de la Rodilla/cirugía , Tapones Quirúrgicos de Gaza , Ingeniería de Tejidos/métodos , Animales , Cartílago Articular/citología , Cartílago Articular/cirugía , Proliferación Celular , Condrocitos/citología , Glicosaminoglicanos/biosíntesis , Imagen por Resonancia Magnética , Conejos , Cicatrización de HeridasRESUMEN
BACKGROUND & OBJECTIVE: Combined therapy has been advocated for modern tumor treatment; the combined target therapy is a valuable research direction. Based on the previous research of nasopharyngeal carcinoma (NPC) radioimmunotherapy, this experiment was designed to develop two immunoconjugates of the monoclonal antibody BAC(5):PYM-BAC(5) and (131)I-BAC(5), and to assess the inhibition effects of their combined treatment on the NPC CNE-2 cells cultured in vitro. METHODS: Dextran T40 was used as media to link PYM and BAC(5). The conjugate PYM-BAC(5) was identified by testing its immunoactivity and the inhibition to mycobacterium. BAC(5) was labeled with (131)I by Chloramin-T method. Five experimental groups were set up:(1)PYM-BAC(5) group, (2)free PYM group, (3)(131)I-BAC(5) group, (4)(131)I-mIgG group, (5)the combined target treatment group ( (131)I-BAC(5)+PYM-BAC(5)). The antitumor effects of the five groups were assessed with MTT method. RESULTS: The 50% inhibition doses(IC(50)) of PYM-BAC(5) group and PYM group were 46.57 microg/ml and 316.7 microg/ml, respectively. The IC(50) of (131)I-BAC(5) group and (131)I-mIgG group to CNE2 were 4.42 x 10(5) Bq/ml and >11.1 x 10(5) Bq/ml,respectively. In the combined target treatment group(PYM-BAC(5)+(131)I-BAC(5)),the IC(50) of PYM-BAC(5) was 7.01 microg/ml and of (131)I-BAC(5) was 0.54 x 10(5) Bq/ml, which much less than other separate treatment groups. CONCLUSION: The inhibition effects of the target treatment ((131)I-BAC(5) and PYM-BAC(5)) on the NPC CNE-2 cells are stronger than non-target treatment (free PYM and (131)I-BAC(5)). The combined target treatment of the two immune ((131)I-BAC(5)+PYM-BAC(5)) conjugates gets stronger inhibition effects than their separate treatment.