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1.
AJR Am J Roentgenol ; 217(3): 664-675, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34259544

RESUMO

OBJECTIVE. The purpose of our study was to develop a radiomics model based on preoperative MRI and clinical information for predicting recurrence-free survival (RFS) in patients with advanced high-grade serous ovarian carcinoma (HGSOC). MATERIALS AND METHODS. This retrospective study enrolled 117 patients with HGSOC, including 90 patients with recurrence and 27 without recurrence; 1046 radiomics features were extracted from T2-weighted images and contrast-enhanced T1-weighted images using a manual segmentation method. L1 regularization-based least absolute shrinkage and selection operator (LASSO) regression was performed to select features, and the synthetic minority oversampling technique (SMOTE) was used to balance our dataset. A support vector machine (SVM) classifier was used to build the classification model. To validate the performance of the proposed models, we applied a leave-one-out cross-validation method to train and test the classifier. Cox proportional hazards regression, Harrell concordance index (C-index), and Kaplan-Meier plots analysis were used to evaluate the associations between radiomics signatures and RFS. RESULTS. The fusion radiomics-based model yielded a significantly higher AUC value of 0.85 in evaluating RFS than the model using contrast-enhanced T1-weighted imaging features alone or T2-weighted imaging features alone (AUC = 0.79 and 0.74 and p = .02 and .01, respectively). Kaplan-Meier survival curves showed significant differences between high and low recurrence risk in patients with HGSOC by different models. The fusion model combining radiomics features and clinical information showed higher performance than the clinical model (C-index = 0.62 and 0.60, respectively). CONCLUSION. The proposed MRI-based radiomics signatures may provide a potential way to develop a prediction model and can help identify patients with advanced HGSOC who have a high risk of recurrence.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Máquina de Vetores de Suporte , Feminino , Humanos , Pessoa de Meia-Idade , Ovário/diagnóstico por imagem , Ovário/patologia , Estudos Retrospectivos , Análise de Sobrevida
2.
Biochem Biophys Res Commun ; 526(2): 512-518, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32245620

RESUMO

The post-transcriptional regulation of gene expression plays an important role in many essential biological processes. The RNA decapping enzyme Dcp2 is a crucial enzyme involved in RNA degradation. Dcp2 proteins are highly expressed in the testis and brain in adult mice. This study aimed to investigate the in vivo functions of Dcp2. An inducible Dcp2 knockout mouse model was established. No obvious health abnormalities were observed after postnatal global deletion of Dcp2 in male mice. However, Dcp2-deleted male mice were infertile and showed Sertoli cell vacuolization and germ cell degeneration. Dcp2 deletion resulted in testicular atrophy, reduced number of epididymal sperm, and increased apoptosis in seminiferous tubules. However, spermatocyte-specific deletion of Dcp2 did not compromise the fertility. The findings of this study indicated that Dcp2 was important for spermatogenesis and male fertility.

3.
Hortic Res ; 6: 100, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31666961

RESUMO

Heat stress is a serious and widespread threat to the quality and yield of many crop species, including grape (Vitis vinifera L.), which is cultivated worldwide. Here, we conducted phosphoproteomic and acetylproteomic analyses of leaves of grape plants cultivated under four distinct temperature regimes. The phosphorylation or acetylation of a total of 1011 phosphoproteins with 1828 phosphosites and 96 acetyl proteins with 148 acetyl sites changed when plants were grown at 35 °C, 40 °C, and 45 °C in comparison with the proteome profiles of plants grown at 25 °C. The greatest number of changes was observed at the relatively high temperatures. Functional classification and enrichment analysis indicated that phosphorylation, rather than acetylation, of serine/arginine-rich splicing factors was involved in the response to high temperatures. This finding is congruent with previous observations by which alternative splicing events occurred more frequently in grapevine under high temperature. Changes in acetylation patterns were more common than changes in phosphorylation patterns in photosynthesis-related proteins at high temperatures, while heat-shock proteins were associated more with modifications involving phosphorylation than with those involving acetylation. Nineteen proteins were identified with changes associated with both phosphorylation and acetylation, which is consistent with crosstalk between these posttranslational modification types.

4.
Am J Cancer Res ; 8(6): 964-980, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30034935

RESUMO

The highly refractory nature of cervical cancer to chemotherapeutic drugs and its epithelial-to-mesenchymal transition (EMT) are the key reasons contributing to the poor prognosis of this disease. Golgi Membrane Protein 1 (GOLM1), a protein involved in the trafficking of proteins through the Golgi apparatus, has been shown to be oncogenic in a variety of human cancers. Herein, we found GOLM1 was markedly up-regulated in cervical cancer and GOLM1 down-expression enhanced the anti-tumor effect of methotrexate. By performing mechanistic studies using both in vitro and in vivo models, we found that GOLM1 could target matrix metallopeptidase 13 (MMP13), a member of the MMPs, and regulate the EMT process. Moreover, altered EMT progression compromised the chemotherapy-enhancing effects of GOLM1 knock-down. Finally, we found significantly higher levels of GOLM1 and MMP13 in cervical cancer tissues compared with adjacent noncancerous tissues, and this was also associated with poor cervical cancer patients' prognosis. Taken together, our results suggest that the GOLM1/MMP13/EMT axis is an important factor involved in regulating methotrexate in cervical cancer, and highlights the potential of novel GOLM1-based clinical modalities as a therapeutic approach in cervical cancer patients.

5.
Biosci Biotechnol Biochem ; 82(10): 1724-1732, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29912646

RESUMO

The RNA decapping enzyme Dcp2 is a crucial enzyme involved in the process of RNA turnover, which can post-transcriptionally regulate gene expression. Dcp2 has been found to be highly expressed in embryonic, but not adult, kidneys. Here we showed that Dcp2 mRNA was expressed, but Dcp2 proteins were absent, in mouse kidneys after postnatal day 10 (P10). In kidneys of adult Dcp2-IRES-EGFP knock-in mice, Dcp2 was undetectable but EGFP was expressed, indicating that Dcp2 mRNA was not completely silenced in adult kidneys. Using luciferase reporter assays, we found that miR-141-3p/200a-3p directly targeted the 3' UTR of Dcp2 mRNA. Overexpression of miR-141-3p and miR-200a-3p downregulated endogenous Dcp2 protein expression. Furthermore, miR-141-3p and miR-200a-3p expression was low in embryonic kidneys but increased dramatically after P10 and was negatively correlated with Dcp2 protein expression during renal development. These results suggest miR-141-3p/200a-3p may be involved in post-transcriptional repression of Dcp2 expression during renal development. ABBREVIATIONS: IRES: internal ribosome entry site; EGFP: enhanced green fluorescent protein; UTR: untranslated region.


Assuntos
Endorribonucleases/genética , Rim/crescimento & desenvolvimento , MicroRNAs/genética , Processamento Pós-Transcricional do RNA , Regiões 3' não Traduzidas , Animais , Inativação Gênica , Células HEK293 , Humanos , Rim/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , RNA Mensageiro/genética
7.
Eur Radiol ; 26(9): 2947-55, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26787604

RESUMO

PURPOSE: To explore the value of in-line phase-contrast imaging with computed tomography (ILPCI-CT) by synchrotron radiation (SR) for liver fibrosis. MATERIALS AND METHODS: Liver fibrosis models were set up in 13 BALB/c mice by peritoneal injections of thioacetamide and evaluated by ILPCI-CT. Histological staging was used to categorize liver fibrosis into normal, mild fibrosis and advanced fibrosis groups. Microvessel density (MVD), the ratio of total vessel length to volume (L/V), the ratio of total number of branching points to liver volume (P/V) and the distribution of vessel diameter were assessed. RESULTS: The CT images showed slightly high-density shadows around the portal tracts in the fibrosis group. Three-dimensional reconstruction can detect vascular and nodular changes on the surface of fibrotic livers. The MVDs between the three groups were significantly different (P = 0.024). L/V was significantly different between the three groups (P = 0.014). There was a positive correlation between MVD and P/V. CONCLUSION: Fibrous material can be detected by ILPCI-CT even in the early stage of fibrosis. MVD, L/V, P/V and the distribution of vessel diameter were consistent with fibrosis-related angiogenesis progress. Three-dimensional reconstruction is a promising method to visualize morphological changes of the fibrotic liver. KEY POINTS: • ILPCI-CT can detect fibrous material even in the early stage of liver fibrosis. • MVD, L/V, P/V, and the distribution of vascular diameter reflect pathological angiogenesis. • 3D reconstruction could be a promising approach for detecting liver fibrosis.


Assuntos
Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Microvasos/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Animais , Modelos Animais de Doenças , Fibrose , Masculino , Camundongos , Camundongos Endogâmicos BALB C
8.
J Biol Chem ; 289(30): 21028-39, 2014 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-24891513

RESUMO

Wnt5a has been found recently to be involved in inflammation regulation through a mechanism that remains unclear. Immunohistochemical staining of infected human dental pulp and tissue from experimental dental pulpitis in rats showed that Wnt5a levels were increased. In vitro, Wnt5a was increased 8-fold in human dental pulp cells (HDPCs) after TNF-α stimulation compared with control cells. We then investigated the role of Wnt5a in HDPCs. In the presence of TNF-α, Wnt5a further increased the production of cytokines/chemokines, whereas Wnt5a knockdown markedly reduced cytokine/ chemokine production induced by TNF-α. In addition, in HDPCs, Wnt5a efficiently induced cytokine/chemokine expression and, in particular, expression of IL-8 (14.5-fold) and CCL2 (25.5-fold), as assessed by a Luminex assay. The cytokine subsets regulated by Wnt5a overlap partially with those induced by TNF-α. However, no TNF-α and IL-1ß was detected after Wnt5a treatment. We then found that Wnt5a alone and the supernatants of Wnt5a-treated HDPCs significantly increased macrophage migration, which supports a role for Wnt5a in macrophage recruitment and as an inflammatory mediator in human dental pulp inflammation. Finally, Wnt5a participates in dental pulp inflammation in a MAPK-dependent (p38-, JNK-, and ERK-dependent) and NF-κB-dependent manner. Our data suggest that Wnt5a, as an inflammatory mediator that drives the integration of cytokines and chemokines, acts downstream of TNF-α.


Assuntos
Polpa Dentária/metabolismo , Mediadores da Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Wnt/metabolismo , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Polpa Dentária/patologia , Feminino , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , NF-kappa B/genética , Proteínas Proto-Oncogênicas/genética , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Wnt/genética , Proteína Wnt-5a
9.
Eur Radiol ; 23(2): 417-23, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22903640

RESUMO

OBJECTIVES: To determine whether phase-contrast X-ray imaging can be used to visualise directly the accumulated extracellular matrix proteins associated with liver fibrosis in common bile duct ligated mice. METHODS: Twenty-six-week-old C57BL female mice were randomised into three groups. In groups 1 (n = 5) and 2 (n = 10), common bile duct ligation was conducted to produce secondary biliary cirrhosis. Mouse livers were then excised 15 (group 1) and 40 days (group 2) after the ligation of the common bile duct for imaging. In the control group, the livers of 5 mice were excised 40 days after the sham operation. Images were then acquired using the analyser crystal set at different positions of the rocking curve. RESULTS: The results show that the fibrotic septa and hepatic lobules enclosed by fibrotic septa can be visualised clearly at the whole organ level via phase-contrast X-ray imaging without any contrast agent. CONCLUSION: These results suggest that phase-contrast X-ray imaging can easily reveal the accumulated extracellular matrix proteins associated with liver fibrosis without using any contrast agent and has great potential in the study of liver fibrosis.


Assuntos
Meios de Contraste , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Radiografia/métodos , Animais , Biópsia por Agulha , Ducto Colédoco/cirurgia , Modelos Animais de Doenças , Feminino , Hepatectomia/métodos , Imuno-Histoquímica , Ligadura , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Valores de Referência , Sensibilidade e Especificidade , Técnicas de Cultura de Tecidos
10.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 25(6): 580-3, 2007 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-18306631

RESUMO

OBJECTIVE: The purpose was to analyze the effects of three sterilization methods (dry heat sterilization, steam sterilization, chemical sterilization) on the corrosion of dental fissure burs. METHODS: 100 dental fissure burs were distributed to 10 groups. One was control, the burs in the other 9 groups were treated by dry heat sterilization, steam sterilization, chemical sterilization with 5, 10, 15 cycles respectively. Weight method, scanning electron microscope, micro-hardness measurement were used to analyze the corrosion of dental fissure burs. RESULTS: The fissure burs gained their weight with cycles of sterilization. 5, 10, 15 cycles of dry heat sterilization, 10, 15 cycles of steam sterilization and 15 cycles of chemical sterilization, the weight of fissure burs were significantly increased (P < 0.05). Scanning electron microscope showed differences on the surfaces of dental fissure burs among the three sterilization groups. After sterilization, spot or partial erosion were seen on the surface of the burs. The steam sterilization groups showed the most evident changes, followed by chemical sterilization groups and dry heat sterilization groups. X-ray energy spectrometer showed the steam sterilization groups had the largest percentage of W, followed by dry heat sterilization groups, chemical sterilization groups and control group. Fe had the opposite trends. Micro-hardness reduced after sterilization. The reduction was most clear in steam sterilization group, followed by chemical sterilization and dry heat sterilization ( P< 0.05). The difference between 5 and 10 times of steam sterilization and 5, 10, 15 times of chemical sterilization were significant difference (P < 0.05). There was no significant difference between 5, 10, 15 times of dry heat sterilization (P > 0.05). CONCLUSION: The corrosion is most severe in steamsterilization group, followed by chemical sterilization, dry heat sterilization. Dry heat sterilization shows less corrosion.


Assuntos
Corrosão , Fissuras Dentárias , Equipamentos Odontológicos de Alta Rotação , Instrumentos Odontológicos , Vapor , Esterilização
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