Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 51
Filtrar
1.
J Magn Reson Imaging ; 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38236785

RESUMO

BACKGROUND: Quantitative in-situ pH mapping of gliomas is important for therapeutic interventions, given its significant association with tumor progression, invasion, and metastasis. Although chemical exchange saturation transfer (CEST) offers a noninvasive way for pH imaging based on the pH-dependent exchange rate (ksw ), the reliable quantification of ksw in glioma remains constrained due to technical challenges. PURPOSE: To quantify the pH of gliomas by measuring the proton exchange rate through optimized omega plot analysis. STUDY TYPE: Prospective. PHANTOMS/ANIMAL MODEL/SUBJECTS: Creatine and murine brain lysates phantoms, six rats with glioma xenograft model, and three patients with World Health Organization grade 2-4 gliomas. FIELD STRENGTH/SEQUENCE: 11.7 T, 7.0 T, CEST imaging, T2 -weighted (T2 W) imaging, and T1 -mapping. ASSESSMENT: Omega plot analysis, quasi-steady-state (QUASS) analysis, multi-pool Lorentzian fitting, amine and amide concentration-independent detection, pH enhanced method with the combination of amide and guanidyl (pHenh ), and magnetization transfer ratio (MTR) were utilized for pH metric quantification. The clinical outcomes were determined through radiologic follow-up and histopathological analysis. STATISTICAL TESTS: Mann-Whitney U test was performed to compare glioma with normal tissue, and Pearson's correlation analysis was used to assess the relationship between ksw and other parameters. RESULTS: In vitro experiments reveal that the determined ksw at 2 ppm increases exponentially with pH (creatine phantoms: ksw = 106 + 0.147 × 10(pH-4.198) ; lysates: ksw = 185.1 + 0.101 × 10(pH-3.914) ). Omega plot analysis exhibits a linear correlation between 1/MTRRex and 1/ω1 2 in the glioma xenografts (R2 > 0.98) and glioma patients (R2 > 0.99). The exchange rate in the rat glioma decreases compared to the contralateral normal tissue (349.46 ± 30.40 s-1 vs. 403.54 ± 51.01 s-1 , P = 0.025), while keeping independence from changes in concentration (r = 0.5037, P = 0.095). Similar pattern was observed in human data. DATA CONCLUSION: Utilizing QUASS-based, spillover-, and MT-corrected omega plot analysis for the measurement of exchange rates, offers a feasible method for quantifying pH within glioma. LEVEL OF EVIDENCE: NA TECHNICAL EFFICACY: Stage 1.

2.
J Magn Reson Imaging ; 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38206839

RESUMO

BACKGROUND: Hemangioblastoma (HB) is a highly vascularized tumor most commonly occurring in the posterior cranial fossa, requiring accurate preoperative diagnosis to avoid accidental intraoperative hemorrhage and even death. PURPOSE: To accurately distinguish HBs from other cerebellar-and-brainstem tumors using a convolutional neural network model based on a contrast-enhanced brain MRI dataset. STUDY TYPE: Retrospective. POPULATION: Four hundred five patients (182 = HBs; 223 = other cerebellar-and brainstem tumors): 305 cases for model training, and 100 for evaluation. FIELD STRENGTH/SEQUENCE: 3 T/contrast-enhanced T1-weighted imaging (T1WI + C). ASSESSMENT: A CNN-based 2D classification network was trained by using sliced data along the z-axis. To improve the performance of the network, we introduced demographic information, various data-augmentation methods and an auxiliary task to segment tumor region. Then, this method was compared with the evaluations performed by experienced and intermediate-level neuroradiologists, and the heatmap of deep feature, which indicates the contribution of each pixel to model prediction, was visualized by Grad-CAM for analyzing the misclassified cases. STATISTICAL TESTS: The Pearson chi-square test and an independent t-test were used to test for distribution difference in age and sex. And the independent t-test was exploited to evaluate the performance between experts and our proposed method. P value <0.05 was considered significant. RESULTS: The trained network showed a higher accuracy for identifying HBs (accuracy = 0.902 ± 0.031, F1 = 0.891 ± 0.035, AUC = 0.926 ± 0.040) than experienced (accuracy = 0.887 ± 0.013, F1 = 0.868 ± 0.011, AUC = 0.881 ± 0.008) and intermediate-level (accuracy = 0.827 ± 0.037, F1 = 0.768 ± 0.068, AUC = 0.810 ± 0.047) neuroradiologists. The recall values were 0.910 ± 0.050, 0.659 ± 0.084, and 0.828 ± 0.019 for the trained network, intermediate and experienced neuroradiologists, respectively. Additional ablation experiments verified the utility of the introduced demographic information, data augmentation, and the auxiliary-segmentation task. DATA CONCLUSION: Our proposed method can successfully distinguish HBs from other cerebellar-and-brainstem tumors and showed diagnostic efficiency comparable to that of experienced neuroradiologists. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38082798

RESUMO

Multi-tile image stitching aims to merge multiple natural or biomedical images into a single mosaic. This is an essential step in whole-slide imaging and large-scale pathological imaging systems. To tackle this task, a multi-step framework is usually used by first estimating the optimal transformation for each image and then fusing them into a whole image. However, the traditional approaches are usually time-consuming and require manual adjustments. Advances in deep learning techniques provide an end-to-end solution to register and fuse information of multiple tile images. In this paper, we present a deep learning model for multi-tile biomedical image stitching, namely MosaicNet, consisting of an aligning network and a fusion network. We trained the MosaicNet network on a large simulation dataset based on the VOC2012 dataset and evaluated the model on multiple types of datasets, including simulated natural images, mouse brain T2-weighted Magnetic Resonance Imaging (T2w-MRI) data, and mouse brain polarization sensitive-optical coherence tomography (PS-OCT) data. Our method outperformed traditional approaches on both natural images and brain imaging data. The proposed method is robust to different settings of hyper-parameters and shows high computational efficiency, up to approximately 32 times faster than the conventional methods.


Assuntos
Aprendizado Profundo , Processamento de Imagem Assistida por Computador , Animais , Camundongos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Simulação por Computador , Encéfalo/diagnóstico por imagem
4.
BMC Womens Health ; 23(1): 487, 2023 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-37705033

RESUMO

BACKGROUND: The objective of the present study was to investigate whether associations exist between inflammatory biomarkers and all-cause mortality and cardiovascular disease (CVD) mortality in women with postmenopausal osteoporosis (PMOP) or osteopenia. METHODS: In this retrospective cohort study, data were obtained from the National Health and Nutrition Examination Survey database from the years 2007 to 2010, 2013 to 2014, and 2017 to 2018. The inflammatory biomarkers including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), neutrophil × platelet/lymphocyte (SII), neutrophil × monocyte/lymphocyte (SIRI), and neutrophil × monocyte × platelet/lymphocyte ratio (AISI) were calculated. RESULTS: A total of 2,834 women were included, with a median survival of 113.51 (3.15) months. During follow-up, 602 women died of all-cause mortality and 185 women died of CVD. NLR, MLR, SIRI, and AISI were significantly associated with all-cause mortality in postmenopausal women with osteoporosis or osteopenia. NLR, MLR, SIRI, and AISI were related to CVD mortality in postmenopausal women with osteoporosis or osteopenia (All P < 0.05). Based on the results of the subgroup analysis, AISI, SIRI, and MLR were associated with all-cause mortality and CVD mortality in postmenopausal women with PMOP or osteopenia who had a history of CVD and diabetes. AISI, SII, MLR, and NLR were associated with all-cause mortality and CVD mortality in PMOP or osteopenia women with a body mass index (BMI) > 25 kg/m2. PLR was associated with all-cause mortality in PMOP or osteopenia women aged ≥ 65 years. CONCLUSION: Inflammatory biomarkers were correlated with mortality risk in the PMOP or osteopenia population. This finding may be helpful for the prognosis management of PMOP or osteopenia in postmenopausal women.


Assuntos
Doenças Ósseas Metabólicas , Doenças Cardiovasculares , Osteoporose Pós-Menopausa , Osteoporose , Feminino , Humanos , Inquéritos Nutricionais , Pós-Menopausa , Estudos Retrospectivos
5.
J Viral Hepat ; 30(6): 489-496, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36807422

RESUMO

In 2020, China conducted a nationwide, sero-epidemiological, cross-sectional survey of viral hepatitis. The stratified multi-stage cluster random sampling method was used to select the permanent population aged 1-69 years, followed by questionnaire survey and sample collection and detection of the serological markers of hepatitis B (HBV) and hepatitis C viruses (HCV). A total of 4747 individuals aged 1-69 years were investigated in Zhejiang Province. The positive rates of hepatitis B surface antigen and anti-HCV were 4.3% and 0%, respectively. Compared to a similar sero-epidemiological survey in 1992, the 2020 survey showed that the HBV infection rate in Zhejiang Province decreased by 56.5%. In both surveys, HBV infection rate increased with age (in 1992, χ2  = 185.866, p = .000; in 2020, χ2  = 1383.836, p = .000). Compared with 1992, the positive anti-HCV rate in those aged 1-69 years in 2020 decreased by 100.0%. This result showed that the HBV vaccine and blood screening to prevent HBV and HCV infection significantly decreased the infection rate of HBV and HCV in the younger generation of Zhejiang province. However, the rate of HBV carriers aged 30-69 years was still high, which underscores the need to strengthen the management and treatment of chronic HBV infection. Hence, Zhejiang province can eliminate the public health threat of viral hepatitis.


Assuntos
Hepatite B , Hepatite C , Humanos , Estudos Soroepidemiológicos , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Hepacivirus , Vírus da Hepatite B , China/epidemiologia , Prevalência , Inquéritos e Questionários , Estudos Transversais , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Lactente , Pré-Escolar , Criança
6.
ROMAN ; 2023: 2359-2365, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38347956

RESUMO

Cooperative robots for intraocular surgery allow surgeons to perform vitreoretinal surgery with high precision and stability. Several robot structural designs have shown capabilities to perform these surgeries. This research investigates the comparative performance of a serial and parallel cooperative-controlled robot in completing a retinal vessel-following task, with a focus on human-robot interaction performance and user experience. Our results indicate that despite differences in robot structure and interaction forces and torques, the two robots exhibited similar levels of performance in terms of general robot-to-patient interaction and average operating time. These findings have implications for the development and implementation of surgical robotics, suggesting that both serial and parallel cooperative-controlled robots can be effective for vitreoretinal surgery tasks.

7.
Chemosphere ; 307(Pt 4): 136118, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36007746

RESUMO

In this article, a novel 2D/2D ultrathin Ti3C2/SnS2 Schottky heterojunctions have been prepared via a facile hydrothermal process. The properties of the heterojunction were fully characterized. The photocatalytic degradation performance of composites was examined by photo-degradation of tetracycline hydrochloride (TC-HCL) under visible light irradiation. Compared with single SnS2, 3% Ti3C2/SnS2 displayed the better performance, the removal rate of TC-HCL reached 87.7% and the kinetic rate constant (k) of the optimal 3% Ti3C2/SnS2 composite was about 2.7 times of that of bare SnS2. The improved photocatalytic activity of Ti3C2/SnS2 is ascribed to the formation of 2D/2D Schottky heterojunction, which promotes the spatial charge separation and increases the surface reactive sites.


Assuntos
Tetraciclina , Titânio , Antibacterianos , Catálise , Luz
8.
iScience ; 25(5): 104227, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35434542

RESUMO

The respective value of clinical data and CT examinations in predicting COVID-19 progression is unclear, because the CT scans and clinical data previously used are not synchronized in time. To address this issue, we collected 119 COVID-19 patients with 341 longitudinal CT scans and paired clinical data, and we developed an AI system for the prediction of COVID-19 deterioration. By combining features extracted from CT and clinical data with our system, we can predict whether a patient will develop severe symptoms during hospitalization. Complementary to clinical data, CT examinations show significant add-on values for the prediction of COVID-19 progression in the early stage of COVID-19, especially in the 6th to 8th day after the symptom onset, indicating that this is the ideal time window for the introduction of CT examinations. We release our AI system to provide clinicians with additional assistance to optimize CT usage in the clinical workflow.

9.
Adv Sci (Weinh) ; 9(7): e2104935, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35023300

RESUMO

Surgeons face challenges in intraoperatively defining margin of brain tumors due to its infiltrative nature. Extracellular acidosis caused by metabolic reprogramming of cancer cells is a reliable marker for tumor infiltrative regions. Although the acidic margin-guided surgery shows promise in improving surgical prognosis, its clinical transition is delayed by having the exogenous probes approved by the drug supervision authority. Here, an intelligent surface-enhanced Raman scattering (SERS) navigation system delineating glioma acidic margins without administration of exogenous probes is reported. With assistance of this system, the metabolites at the tumor cutting edges can be nondestructively transferred within a water droplet to a SERS chip with pH sensitivity. Homemade deep learning model automatically processes the Raman spectra collected from the SERS chip and delineates the pH map of tumor resection bed with increased speed. Acidity correlated cancer cell density and proliferation level are demonstrated in tumor cutting edges of animal models and excised tissues from glioma patients. The overall survival of animal models post the SERS system guided surgery is significantly increased in comparison to the conventional strategy used in clinical practice. This SERS system holds the promise in accelerating clinical transition of acidic margin-guided surgery for solid tumors with infiltrative nature.


Assuntos
Acidose , Neoplasias Encefálicas , Glioma , Animais , Neoplasias Encefálicas/cirurgia , Glioma/patologia , Glioma/cirurgia , Humanos , Margens de Excisão , Análise Espectral Raman
10.
Cancer Res ; 81(23): 5919-5934, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34580061

RESUMO

Tumor-initiating cells (TIC) are associated with tumor initiation, growth, metastasis, and recurrence. Aldehyde dehydrogenase 1A1 (ALDH1A1) is a TIC marker in many cancers, including breast cancer. However, the molecular mechanisms underlying ALDH1A1 functions in solid tumors remain largely unknown. Here we demonstrate that ALDH1A1 enzymatic activity facilitates breast tumor growth. Mechanistically, ALDH1A1 decreased the intracellular pH in breast cancer cells to promote phosphorylation of TAK1, activate NFκB signaling, and increase the secretion of GM-CSF, which led to myeloid-derived suppressor cell expansion and immunosuppression. Furthermore, the ALDH1A1 inhibitor disulfiram and chemotherapeutic agent gemcitabine cooperatively inhibited breast tumor growth and tumorigenesis by purging ALDH+ TICs and activating T-cell immunity. These findings elucidate how active ALDH1A1 modulates the immune system to promote tumor development, highlighting new therapeutic strategies for malignant breast cancer. SIGNIFICANCE: ALDH1A1 enzyme activity induces MDSC expansion and triggers a procancer immune microenvironment to facilitate breast cancer progression, providing a novel therapeutic vulnerability in this disease.


Assuntos
Família Aldeído Desidrogenase 1/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/patologia , Tolerância Imunológica , Células Supressoras Mieloides/imunologia , Células-Tronco Neoplásicas/patologia , Retinal Desidrogenase/metabolismo , Microambiente Tumoral , Família Aldeído Desidrogenase 1/genética , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Movimento Celular , Proliferação de Células , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Regulação Neoplásica da Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Proteínas Recombinantes/administração & dosagem , Retinal Desidrogenase/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina
11.
Front Oncol ; 11: 679952, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195080

RESUMO

The segmentation of high-grade gliomas (HGG) using magnetic resonance imaging (MRI) data is clinically meaningful in neurosurgical practice, but a challenging task. Currently, most segmentation methods are supervised learning with labeled training sets. Although these methods work well in most cases, they typically require time-consuming manual labeling and pre-trained models. In this work, we propose an automatically unsupervised segmentation toolbox based on the clustering algorithm and morphological processing, named AUCseg. With our toolbox, the whole tumor was first extracted by clustering on T2-FLAIR images. Then, based on the mask acquired with whole tumor segmentation, the enhancing tumor was segmented on the post-contrast T1-weighted images (T1-CE) using clustering methods. Finally, the necrotic regions were segmented by morphological processing or clustering on T2-weighted images. Compared with K-means, Mini-batch K-means, and Fuzzy C Means (FCM), the Gaussian Mixture Model (GMM) clustering performs the best in our toolbox. We did a multi-sided evaluation of our toolbox in the BraTS2018 dataset and demonstrated that the whole tumor, tumor core, and enhancing tumor can be automatically segmented using default hyper-parameters with Dice score 0.8209, 0.7087, and 0.7254, respectively. The computing time of our toolbox for each case is around 22 seconds, which is at least 3 times faster than other state-of-the-art unsupervised methods. In addition, our toolbox has an option to perform semi-automatic segmentation via manually setup hyper-parameters, which could improve the segmentation performance. Our toolbox, AUCseg, is publicly available on Github. (https://github.com/Haifengtao/AUCseg).

12.
Int J Nanomedicine ; 16: 741-752, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33564233

RESUMO

BACKGROUND: Quercetin has potential value in treating cardiovascular diseases, but it is not suitable for clinical application due to its own water solubility. The limitation of quercetin can be distinctly ameliorated by delivering it with nanocarriers. OBJECTIVE: To determine the effect of quercetin-loaded mesoporous silica nanoparticles (Q-MSNs) on myocardial ischemia-reperfusion injury in rats and its mechanism. METHODS: Q-MSNs were synthesized, and the morphology of Q-MSNs and MSNs was characterized by transmission electron microscopy and dynamic light scattering technique, respectively. Healthy rats were enrolled and randomly divided into a sham operation control group, an ischemia-reperfusion (IR) group, an IR+Q group, an IR+Q-MSNs group, and an MSNs group (each n = 10). Rats in the sham operation group were not treated with ischemia reperfusion, but given normal perfusion meantime. Rats in the sham operation control group, IR group, and MSNs group were given normal saline for 10 days before ischemia reperfusion, and rats in the IR+Q group and IR+Q-MSNs group were given drugs by gavage for 10 days before ischemia reperfusion. Primary myocardial cells were sampled from SD neonatal rats to construct hypoxia/reoxygenation myocardial cell models. The myocardial cells were assigned to a control group, IR group, quercetin (Q) group, Q-MSNs group, and MSNs group. Except for the control group, all the other groups were treated with hypoxia/reoxygenation. Cells in the Q group were treated with quercetin (10 µM, 20 µM, 40 µM) for 24 h in advance and then treated with measures to cause hypoxia-reoxygenation injury. Cells in the Q-MSNs group were treated with the same concentration of loaded quercetin and the same method used for the Q group. The myocardial apoptosis, myocardial infarction, ventricular remodeling, hemodynamic indexes, physiological and biochemical indexes, and JAK2/STAT3 pathway expression of each group were detected, and the apoptosis, viability, oxidative stress, and JAK2/STAT3 pathway expression of primary myocardial cells in each group were also detected. RESULTS: Quercetin significantly activated the JAK2/STAT3 pathway in vivo and in vitro, and MSNs intensified the activation. Compared with quercetin, Q-MSNs were more effective in inhibiting cell apoptosis and oxidative stress, reducing myocardial infarction size, improving ventricular remodeling and cardiac function-related biochemical indexes, and promoting the recovery of cardiac blood flow. CONCLUSION: Q-MSNs can significantly enhance the activation effect of quercetin on JAK2/STAT3 pathway, thus enhancing its protection on the heart of MIRI rats.


Assuntos
Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Nanopartículas/química , Quercetina/uso terapêutico , Dióxido de Silício/química , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Liberação Controlada de Fármacos , Hemodinâmica/efeitos dos fármacos , Janus Quinases/metabolismo , Cinética , Masculino , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Nanopartículas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Porosidade , Quercetina/farmacologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
14.
IUBMB Life ; 71(12): 1906-1915, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31317647

RESUMO

piRNAs are a large class of small noncoding RNA that interact with an animal-specific class of Argonaute proteins, P-element induced wimpy proteins. piRNAs were initially discovered in mouse testes to be a fundamental component of spermatogenesis. Outside of the germline, piRNAs were found to function in embryogenesis, development, regeneration and cancer cells. However, despite a decade of scrutiny, functional understanding of this class of small RNAs remains very limited. To determine whether there are piRNAs present and involved in the cellular reprogramming process, we extracted piwi-interacting RNA (piRNA) signatures from a small RNA deep sequencing data set of mouse embryonic fibroblasts (MEFs), mouse embryonic stem cells (mESCs) and reprogrammed stem cells by three different technologies. We successfully identified three piRNA families specifically expressed in these reprogrammed stem cells. Meanwhile, there were almost no piRNAs observed in MEFs and mESCs. Further analysis indicated that these piRNAs may associate with the reprogramming process but not cellular pluripotency. Target gene prediction suggested that at least one of piRNAs, piR-mmu-64162, may take part in the reprogramming process by regulating cell senescence. Overall, we firstly identified the potential reprogramming associated piRNAs, shedding new light on piRNA functions.


Assuntos
Fibroblastos/citologia , Células-Tronco Pluripotentes Induzidas/fisiologia , RNA Interferente Pequeno/genética , Animais , Embrião de Mamíferos/citologia , Fibroblastos/fisiologia , Regulação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Células-Tronco Pluripotentes Induzidas/citologia , Camundongos
15.
J Microbiol Biotechnol ; 28(11): 1876-1882, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30562883

RESUMO

A series of pentacyclic triterpenoids similar to glycyrrhetinic acid were designed and synthesized via the combination of chemical modification and microbial catalysis. All products were screened for the glycogen phosphorylases inhibitory activities in vitro. Within this series of derivatives, compound 5 displayed good inhibitory activities with IC50 value of 27.7 µM, which is better than that of the other derivatives and glycyrrhetinic acid. Structure-activity relationship (SAR) analysis of these inhibitors was also discussed.


Assuntos
Aspergillus ochraceus/metabolismo , Glicogênio Fosforilase/antagonistas & inibidores , Ácido Oleanólico , Streptomyces griseus/metabolismo , Biotransformação , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/química , Concentração Inibidora 50 , Estrutura Molecular , Ácido Oleanólico/biossíntese , Ácido Oleanólico/síntese química , Ácido Oleanólico/química , Ácido Oleanólico/metabolismo , Relação Estrutura-Atividade
16.
Acta Biochim Biophys Sin (Shanghai) ; 49(7): 635-642, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28510621

RESUMO

Mouse miR-290 cluster miRNAs are expressed specifically in early embryos and embryonic germ cells. These miRNAs play critical roles in the maintenance of pluripotency and self-renewal. Here, we showed that Cyclin D1 is a direct target gene of miR-290 cluster miRNAs. Negative relationships between the expression of Cyclin D1 protein and miR-290 cluster miRNAs in pluripotent and non-pluripotent cells, as well as in differentiating CGR8 cells were observed. Inhibition of miR-290 cluster miRNAs could arrest cells at the G1 phase and slow down the cell proliferation in CGR8 mouse stem cells. Since miR-290 cluster miRNAs are the most dominant stem-cell-specific miRNAs, our results revealed an important cause for the absence of Cyclin D1 in mouse embryonic stem cells.


Assuntos
Ciclina D1/análise , MicroRNAs/fisiologia , Células-Tronco Embrionárias Murinas/química , Animais , Proliferação de Células , Células Cultivadas , Ciclina D1/genética , Quinase 4 Dependente de Ciclina/fisiologia , Quinase 6 Dependente de Ciclina/fisiologia , Fase G1 , Camundongos , Células-Tronco Embrionárias Murinas/citologia
17.
J Clin Invest ; 126(5): 1801-14, 2016 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-27043280

RESUMO

Aberrant vascularization is a hallmark of cancer progression and treatment resistance. Here, we have shown that endothelial cell (EC) plasticity drives aberrant vascularization and chemoresistance in glioblastoma multiforme (GBM). By utilizing human patient specimens, as well as allograft and genetic murine GBM models, we revealed that a robust endothelial plasticity in GBM allows acquisition of fibroblast transformation (also known as endothelial mesenchymal transition [Endo-MT]), which is characterized by EC expression of fibroblast markers, and determined that a prominent population of GBM-associated fibroblast-like cells have EC origin. Tumor ECs acquired the mesenchymal gene signature without the loss of EC functions, leading to enhanced cell proliferation and migration, as well as vessel permeability. Furthermore, we identified a c-Met/ETS-1/matrix metalloproteinase-14 (MMP-14) axis that controls VE-cadherin degradation, Endo-MT, and vascular abnormality. Pharmacological c-Met inhibition induced vessel normalization in patient tumor-derived ECs. Finally, EC-specific KO of Met inhibited vascular transformation, normalized blood vessels, and reduced intratumoral hypoxia, culminating in suppressed tumor growth and prolonged survival in GBM-bearing mice after temozolomide treatment. Together, these findings illustrate a mechanism that controls aberrant tumor vascularization and suggest that targeting Endo-MT may offer selective and efficient strategies for antivascular and vessel normalization therapies in GBM, and possibly other malignant tumors.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Células Endoteliais/metabolismo , Glioblastoma/irrigação sanguínea , Glioblastoma/metabolismo , Neovascularização Patológica/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Animais , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/genética , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Dacarbazina/análogos & derivados , Dacarbazina/farmacologia , Células Endoteliais/patologia , Feminino , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Humanos , Masculino , Metaloproteinase 14 da Matriz/genética , Metaloproteinase 14 da Matriz/metabolismo , Camundongos , Camundongos Knockout , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Proteína Proto-Oncogênica c-ets-1/genética , Proteína Proto-Oncogênica c-ets-1/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Temozolomida
18.
Comput Math Methods Med ; 2015: 848079, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26495035

RESUMO

The objective of this study is to analyze the biomechanical effects of sinuses in the skull on the facial impact response. Two models were built, where one had sinuses and the other had none. The models were verified using cadaver test data, including impacts to frontal bone, zygomatic bone, and maxillae. In the maxilla and zygoma impact, sinuses were found to have no significant effect on the global distribution of stress or stiffness of facial bones, and the influence was limited in local area. In forehead impact, the sinuses significantly affected the distribution of stress and strain in the skull due to its location in facial bones. The result shows that if the sinus is far away from the location of impact, its effect on the overall response of skull could be ignored. In addition, the distance between the region of interest and sinuses is another important parameter when studying the local effect of sinuses.


Assuntos
Traumatismos Cranianos Fechados/fisiopatologia , Modelos Biológicos , Seios Paranasais/fisiopatologia , Crânio/lesões , Crânio/fisiopatologia , Fenômenos Biomecânicos , Elasticidade , Ossos Faciais/lesões , Ossos Faciais/patologia , Ossos Faciais/fisiopatologia , Análise de Elementos Finitos , Traumatismos Cranianos Fechados/patologia , Humanos , Imageamento Tridimensional , Modelos Anatômicos , Seios Paranasais/patologia , Crânio/patologia , Estresse Mecânico , Viscosidade
19.
Acta Biochim Biophys Sin (Shanghai) ; 47(8): 630-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26124189

RESUMO

MicroRNAs play important roles in carcinogenesis and tumor progress. Lung cancer is the leading cause of cancer mortality worldwide. In this study, the function of miR-181a-5p was investigated in non-small-cell lung cancer (NSCLC). Results showed that miR-181a-5p was significantly decreased in NSCLC tissues and cell lines. The proliferation and migration of A549 cells transfected with miR-181a-5p mimic was significantly inhibited. Luciferase activity assay results demonstrated that two binding sites of Kras could be directly targeted by miR-181a-5p. Furthermore, Kras was down-regulated by miR-181a-5p at both transcriptional and translational levels. SiRNA-mediated Kras down-regulation could mimic the effects of miR-181a-5p mimic in A549 cells. Our findings suggest that miR-181a-5p plays a potential role in tumor suppression by partially targeting Kras and has the potential therapeutic application in NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Terapia de Alvo Molecular , Transfecção
20.
Oncotarget ; 6(24): 20111-20, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-26036635

RESUMO

Tanshinone is the liposoluble constituent of Salia miltiorrhiza, a root used in traditional herbal medicine which is known to possess certain health benefits. Although it is known that tanshinones, including tanshinone I (T1), tanshinone IIA (T2A), and cryptotanshinone (CT), can inhibit the growth of lung cancer cells in vitro, the mechanism under which they act is still unclear. AURKA, an oncogene, encodes a serine-threonine kinase which regulates mitotic processes in mammalian cells. Here, we reported that tanshinones mediate AURKA suppression partly through up-regulating the expression of miR-32. We found that tanshinones could inhibit cell proliferation, promote apoptosis, and impede cell-cycle progression, thus performing an antineoplastic function in non-small cell lung cancer (NSCLC). Additionally, we demonstrated that tanshinones attained these effects in part by down-regulating AURKA, corroborating previous reports. Our results showed that in NSCLC, similar effects were obtained with knock-down of the AURKA gene by siRNA. We also verified that AURKA was the direct target of miR-32. Collectively, our results demonstrated that tanshinones could inhibit NSCLC by suppressing AURKA via up-regulating the expressions of miR-32 and other related miRNAs.


Assuntos
Abietanos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Aurora Quinase A/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , MicroRNAs/metabolismo , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células HEK293 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/biossíntese , MicroRNAs/genética , Regulação para Cima/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA