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1.
J Comput Assist Tomogr ; 48(3): 498-507, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38438336

RESUMO

OBJECTIVE: The preoperative prediction of the overall survival (OS) status of patients with head and neck cancer (HNC) is significant value for their individualized treatment and prognosis. This study aims to evaluate the impact of adding 3D deep learning features to radiomics models for predicting 5-year OS status. METHODS: Two hundred twenty cases from The Cancer Imaging Archive public dataset were included in this study; 2212 radiomics features and 304 deep features were extracted from each case. The features were selected by univariate analysis and the least absolute shrinkage and selection operator, and then grouped into a radiomics model containing Positron Emission Tomography /Computed Tomography (PET/CT) radiomics features score, a deep model containing deep features score, and a combined model containing PET/CT radiomics features score +3D deep features score. TumorStage model was also constructed using initial patient tumor node metastasis stage to compare the performance of the combined model. A nomogram was constructed to analyze the influence of deep features on the performance of the model. The 10-fold cross-validation of the average area under the receiver operating characteristic curve and calibration curve were used to evaluate performance, and Shapley Additive exPlanations (SHAP) was developed for interpretation. RESULTS: The TumorStage model, radiomics model, deep model, and the combined model achieved areas under the receiver operating characteristic curve of 0.604, 0.851, 0.840, and 0.895 on the train set and 0.571, 0.849, 0.832, and 0.900 on the test set. The combined model showed better performance of predicting the 5-year OS status of HNC patients than the radiomics model and deep model. The combined model was shown to provide a favorable fit in calibration curves and be clinically useful in decision curve analysis. SHAP summary plot and SHAP The SHAP summary plot and SHAP force plot visually interpreted the influence of deep features and radiomics features on the model results. CONCLUSIONS: In predicting 5-year OS status in patients with HNC, 3D deep features could provide richer features for combined model, which showed outperformance compared with the radiomics model and deep model.


Assuntos
Aprendizado Profundo , Neoplasias de Cabeça e Pescoço , Nomogramas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Idoso , Imageamento Tridimensional/métodos , Adulto , Estudos Retrospectivos , Radiômica
2.
BMC Med Imaging ; 24(1): 137, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844854

RESUMO

BACKGROUND: This study investigated whether the Combat compensation method can remove the variability of radiomic features extracted from different scanners, while also examining its impact on the subsequent predictive performance of machine learning models. MATERIALS AND METHODS: 135 CT images of Credence Cartridge Radiomic phantoms were collected and screened from three scanners manufactured by Siemens, Philips, and GE. 100 radiomic features were extracted and 20 radiomic features were screened according to the Lasso regression method. The radiomic features extracted from the rubber and resin-filled regions in the cartridges were labeled into different categories for evaluating the performance of the machine learning model. Radiomics features were divided into three groups based on the different scanner manufacturers. The radiomic features were randomly divided into training and test sets with a ratio of 8:2. Five machine learning models (lasso, logistic regression, random forest, support vector machine, neural network) were employed to evaluate the impact of Combat on radiomic features. The variability among radiomic features were assessed using analysis of variance (ANOVA) and principal component analysis (PCA). Accuracy, precision, recall, and area under the receiver curve (AUC) were used as evaluation metrics for model classification. RESULTS: The principal component and ANOVA analysis results show that the variability of different scanner manufacturers in radiomic features was removed (P˃0.05). After harmonization with the Combat algorithm, the distributions of radiomic features were aligned in terms of location and scale. The performance of machine learning models for classification improved, with the Random Forest model showing the most significant enhancement. The AUC value increased from 0.88 to 0.92. CONCLUSIONS: The Combat algorithm has reduced variability in radiomic features from different scanners. In the phantom CT dataset, it appears that the machine learning model's classification performance may have improved after Combat harmonization. However, further investigation and validation are required to fully comprehend Combat's impact on radiomic features in medical imaging.


Assuntos
Aprendizado de Máquina , Imagens de Fantasmas , Humanos , Tomografia Computadorizada por Raios X , Tomógrafos Computadorizados , Análise de Componente Principal , Redes Neurais de Computação , Algoritmos , Radiômica
3.
J Clin Microbiol ; 59(2)2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33148709

RESUMO

Bacterial vaginosis (BV) is caused by the excessive and imbalanced growth of bacteria in vagina, affecting 30 to 50% of women. Gram staining followed by Nugent scoring based on bacterial morphotypes under the microscope is considered the gold standard for BV diagnosis; this method is often labor-intensive and time-consuming, and results vary from person to person. We developed and optimized a convolutional neural network (CNN) model and evaluated its ability to automatically identify and classify three categories of Nugent scores from microscope images. The CNN model was first established with a panel of microscopic images with Nugent scores determined by experts. The model was trained by minimizing the cross-entropy loss function and optimized by using a momentum optimizer. The separate test sets of images collected from three hospitals were evaluated by the CNN model. The CNN model consisted of 25 convolutional layers, 2 pooling layers, and a fully connected layer. The model obtained 82.4% sensitivity and 96.6% specificity with the 5,815 validation images when altered vaginal flora and BV were considered the positive samples, which was better than the rates achieved by top-level technologists and obstetricians in China. The capability of our model for generalization was so strong that it exhibited 75.1% accuracy in three categories of Nugent scores on the independent test set of 1,082 images, which was 6.6% higher than the average of three technologists, who are hold bachelor's degrees in medicine and are qualified to make diagnostic decisions. When three technologists ran one specimen in triplicate, the precision of three categories of Nugent scores was 54.0%. One hundred three samples diagnosed by two technologists on different days showed a repeatability of 90.3%. The CNN model outperformed human health care practitioners in terms of accuracy and stability for three categories of Nugent score diagnosis. The deep learning model may offer translational applications in automating diagnosis of bacterial vaginosis with proper supporting hardware.


Assuntos
Vaginose Bacteriana , Bactérias , China , Feminino , Humanos , Redes Neurais de Computação , Vagina , Vaginose Bacteriana/diagnóstico
4.
Int J Mol Sci ; 22(21)2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34769308

RESUMO

The retina is a light-sensing ocular tissue that sends information to the brain to enable vision. The blood-retinal barrier (BRB) contributes to maintaining homeostasis in the retinal microenvironment by selectively regulating flux of molecules between systemic circulation and the retina. Maintaining such physiological balance is fundamental to visual function by facilitating the delivery of nutrients and oxygen and for protection from blood-borne toxins. The inner BRB (iBRB), composed mostly of inner retinal vasculature, controls substance exchange mainly via transportation processes between (paracellular) and through (transcellular) the retinal microvascular endothelium. Disruption of iBRB, characterized by retinal edema, is observed in many eye diseases and disturbs the physiological quiescence in the retina's extracellular space, resulting in vision loss. Consequently, understanding the mechanisms of iBRB formation, maintenance, and breakdown is pivotal to discovering potential targets to restore function to compromised physiological barriers. These unraveled targets can also inform potential drug delivery strategies across the BRB and the blood-brain barrier into retinas and brain tissues, respectively. This review summarizes mechanistic insights into the development and maintenance of iBRB in health and disease, with a specific focus on the Wnt signaling pathway and its regulatory role in both paracellular and transcellular transport across the retinal vascular endothelium.


Assuntos
Barreira Hematorretiniana/metabolismo , Permeabilidade Capilar , Vasos Retinianos/fisiologia , Via de Sinalização Wnt , Animais , Transporte Biológico , Humanos
5.
Appl Soft Comput ; 98: 106897, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33199977

RESUMO

The sudden outbreak of novel coronavirus 2019 (COVID-19) increased the diagnostic burden of radiologists. In the time of an epidemic crisis, we hope artificial intelligence (AI) to reduce physician workload in regions with the outbreak, and improve the diagnosis accuracy for physicians before they could acquire enough experience with the new disease. In this paper, we present our experience in building and deploying an AI system that automatically analyzes CT images and provides the probability of infection to rapidly detect COVID-19 pneumonia. The proposed system which consists of classification and segmentation will save about 30%-40% of the detection time for physicians and promote the performance of COVID-19 detection. Specifically, working in an interdisciplinary team of over 30 people with medical and/or AI background, geographically distributed in Beijing and Wuhan, we are able to overcome a series of challenges (e.g. data discrepancy, testing time-effectiveness of model, data security, etc.) in this particular situation and deploy the system in four weeks. In addition, since the proposed AI system provides the priority of each CT image with probability of infection, the physicians can confirm and segregate the infected patients in time. Using 1,136 training cases (723 positives for COVID-19) from five hospitals, we are able to achieve a sensitivity of 0.974 and specificity of 0.922 on the test dataset, which included a variety of pulmonary diseases.

6.
Int J Mol Sci ; 21(4)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32054022

RESUMO

The aim of the current study was to investigate the impact of long-acting fibroblast growth factor 21 (FGF21) on retinal vascular leakage utilizing machine learning and to clarify the mechanism underlying the protection. To assess the effect on retinal vascular leakage, C57BL/6J mice were pre-treated with long-acting FGF21 analog or vehicle (Phosphate Buffered Saline; PBS) intraperitoneally (i.p.) before induction of retinal vascular leakage with intravitreal injection of mouse (m) vascular endothelial growth factor 164 (VEGF164) or PBS control. Five hours after mVEGF164 injection, we retro-orbitally injected Fluorescein isothiocyanate (FITC) -dextran and quantified fluorescence intensity as a readout of vascular leakage, using the Image Analysis Module with a machine learning algorithm. In FGF21- or vehicle-treated primary human retinal microvascular endothelial cells (HRMECs), cell permeability was induced with human (h) VEGF165 and evaluated using FITC-dextran and trans-endothelial electrical resistance (TEER). Western blots for tight junction markers were performed. Retinal vascular leakage in vivo was reduced in the FGF21 versus vehicle- treated mice. In HRMECs in vitro, FGF21 versus vehicle prevented hVEGF-induced increase in cell permeability, identified with FITC-dextran. FGF21 significantly preserved TEER compared to hVEGF. Taken together, FGF21 regulates permeability through tight junctions; in particular, FGF21 increases Claudin-1 protein levels in hVEGF-induced HRMECs. Long-acting FGF21 may help reduce retinal vascular leakage in retinal disorders and machine learning assessment can help to standardize vascular leakage quantification.


Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/farmacologia , Retina/efeitos dos fármacos , Vasos Retinianos/efeitos dos fármacos , Animais , Barreira Hematorretiniana/efeitos dos fármacos , Barreira Hematorretiniana/metabolismo , Barreira Hematorretiniana/patologia , Células Cultivadas , Feminino , Fatores de Crescimento de Fibroblastos/administração & dosagem , Humanos , Aprendizado de Máquina , Masculino , Camundongos Endogâmicos C57BL , Retina/metabolismo , Retina/patologia , Vasos Retinianos/metabolismo , Vasos Retinianos/patologia
7.
Int J Mol Sci ; 21(4)2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32098361

RESUMO

The tightly structured neural retina has a unique vascular network comprised of three interconnected plexuses in the inner retina (and choroid for outer retina), which provide oxygen and nutrients to neurons to maintain normal function. Clinical and experimental evidence suggests that neuronal metabolic needs control both normal retinal vascular development and pathological aberrant vascular growth. Particularly, photoreceptors, with the highest density of mitochondria in the body, regulate retinal vascular development by modulating angiogenic and inflammatory factors. Photoreceptor metabolic dysfunction, oxidative stress, and inflammation may cause adaptive but ultimately pathological retinal vascular responses, leading to blindness. Here we focus on the factors involved in neurovascular interactions, which are potential therapeutic targets to decrease energy demand and/or to increase energy production for neovascular retinal disorders.


Assuntos
Células Fotorreceptoras de Vertebrados/metabolismo , Retina/metabolismo , Doenças Retinianas/metabolismo , Neovascularização Retiniana/metabolismo , Vasos Retinianos/metabolismo , Animais , Velocidade do Fluxo Sanguíneo , Humanos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Doenças Retinianas/fisiopatologia , Neovascularização Retiniana/fisiopatologia , Vasos Retinianos/fisiologia
8.
Bioorg Med Chem Lett ; 29(23): 126709, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629632

RESUMO

Four series of berberine derivatives were designed and synthesized. All the synthetic compounds were screened for in vitro glucose consumption activity in HepG2 cell lines. The results showed that most of the tested compounds exhibited potent hypoglycemic activity, and the most potent compound 20b exhibited its potency by 3.23-fold of berberine, 1.39-fold of metformin and 1.20-fold of rosiglitazone, respectively. Western blot assay indicated these novel berberine-based derivatives executed their glucose-decreasing activity via the activation of AMPK pathway.


Assuntos
Berberina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Berberina/análogos & derivados , Berberina/farmacologia , Humanos , Hipoglicemiantes/farmacologia
9.
FASEB J ; 31(11): 4665-4681, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28739642

RESUMO

Pathological angiogenesis in the eye is an important feature in the pathophysiology of many vision-threatening diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, as well as corneal diseases with abnormal angiogenesis. Development of reproducible and reliable animal models of ocular angiogenesis has advanced our understanding of both the normal development and the pathobiology of ocular neovascularization. These models have also proven to be valuable experimental tools with which to easily evaluate potential antiangiogenic therapies beyond eye research. This review summarizes the current available animal models of ocular angiogenesis. Models of retinal and choroidal angiogenesis, including oxygen-induced retinopathy, laser-induced choroidal neovascularization, and transgenic mouse models with deficient or spontaneous retinal/choroidal neovascularization, as well as models with induced corneal angiogenesis, are widely used to investigate the molecular and cellular basis of angiogenic mechanisms. Theoretical concepts and experimental protocols of these models are outlined, as well as their advantages and potential limitations, which may help researchers choose the most suitable models for their investigative work.-Liu, C.-H., Wang, Z., Sun, Y., Chen, J. Animal models of ocular angiogenesis: from development to pathologies.


Assuntos
Neovascularização de Coroide , Retinopatia Diabética , Modelos Animais de Doenças , Neovascularização Retiniana , Animais , Neovascularização de Coroide/genética , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Neovascularização de Coroide/fisiopatologia , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Retinopatia Diabética/fisiopatologia , Humanos , Camundongos , Camundongos Transgênicos , Neovascularização Retiniana/genética , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/patologia , Neovascularização Retiniana/fisiopatologia
10.
FASEB J ; 31(10): 4492-4502, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28646017

RESUMO

Pathological proliferation of retinal blood vessels commonly causes vision impairment in proliferative retinopathies, including retinopathy of prematurity. Dysregulated crosstalk between the vasculature and retinal neurons is increasingly recognized as a major factor contributing to the pathogenesis of vascular diseases. Class 3 semaphorins (SEMA3s), a group of neuron-secreted axonal and vascular guidance factors, suppress pathological vascular growth in retinopathy. However, the upstream transcriptional regulators that mediate the function of SEMA3s in vascular growth are poorly understood. Here we showed that retinoic acid receptor-related orphan receptor α (RORα), a nuclear receptor and transcription factor, is a novel transcriptional regulator of SEMA3E-mediated neurovascular coupling in a mouse model of oxygen-induced proliferative retinopathy. We found that genetic deficiency of RORα substantially induced Sema3e expression in retinopathy. Both RORα and SEMA3E were expressed in retinal ganglion cells. RORα directly bound to a specific ROR response element on the promoter of Sema3e and negatively regulated Sema3e promoter-driven luciferase expression. Suppression of Sema3e using adeno-associated virus 2 carrying short hairpin RNA targeting Sema3e promoted disoriented pathological neovascularization and partially abolished the inhibitory vascular effects of RORα deficiency in retinopathy. Our findings suggest that RORα is a novel transcriptional regulator of SEMA3E-mediated neurovascular coupling in pathological retinal angiogenesis.-Sun, Y., Liu, C.-H., Wang, Z., Meng, S. S., Burnim, S. B., SanGiovanni, J. P., Kamenecka, T. M., Solt, L. A., Chen, J. RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis.


Assuntos
Glicoproteínas/genética , Proteínas de Membrana/genética , Neovascularização Patológica/metabolismo , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Neovascularização Retiniana/metabolismo , Vasos Retinianos/metabolismo , Animais , Moléculas de Adesão Celular Neuronais/metabolismo , Proteínas do Citoesqueleto , Células Endoteliais/metabolismo , Glicoproteínas/metabolismo , Proteínas de Membrana/metabolismo , Camundongos Transgênicos , Neovascularização Patológica/genética , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Células Ganglionares da Retina , Neovascularização Retiniana/genética , Semaforinas
11.
Am J Pathol ; 186(10): 2588-600, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27524797

RESUMO

Familial exudative vitreoretinopathy (FEVR) is characterized by delayed retinal vascular development, which promotes hypoxia-induced pathologic vessels. In severe cases FEVR may lead to retinal detachment and visual impairment. Genetic studies linked FEVR with mutations in Wnt signaling ligand or receptors, including low-density lipoprotein receptor-related protein 5 (LRP5) gene. Here, we investigated ocular pathologies in a Lrp5 knockout (Lrp5(-/-)) mouse model of FEVR and explored whether treatment with a pharmacologic Wnt activator lithium could bypass the genetic defects, thereby protecting against eye pathologies. Lrp5(-/-) mice displayed significantly delayed retinal vascular development, absence of deep layer retinal vessels, leading to increased levels of vascular endothelial growth factor and subsequent pathologic glomeruloid vessels, as well as decreased inner retinal visual function. Lithium treatment in Lrp5(-/-) mice significantly restored the delayed development of retinal vasculature and the intralaminar capillary networks, suppressed formation of pathologic glomeruloid structures, and promoted hyaloid vessel regression. Moreover, lithium treatment partially rescued inner-retinal visual function and increased retinal thickness. These protective effects of lithium were largely mediated through restoration of canonical Wnt signaling in Lrp5(-/-) retina. Lithium treatment also substantially increased vascular tubular formation in LRP5-deficient endothelial cells. These findings suggest that pharmacologic activation of Wnt signaling may help treat ocular pathologies in FEVR and potentially other defective Wnt signaling-related diseases.


Assuntos
Lítio/farmacologia , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Doenças Retinianas/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Oftalmopatias Hereditárias , Vitreorretinopatias Exsudativas Familiares , Feminino , Humanos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação , Retina/efeitos dos fármacos , Retina/embriologia , Doenças Retinianas/genética , Doenças Retinianas/patologia , Vasos Retinianos/efeitos dos fármacos , Vasos Retinianos/embriologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Opt Express ; 25(22): 26638-26650, 2017 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-29092152

RESUMO

Optomechanics describes the interaction between the optical field and mechanics, and the optomechanical system provides an ideal interface between photons and phonons. The role of the electromagnetic field during optomechanical interaction is studied in this paper as it is regarded as a phonon transmission medium. An analytical model is built to study the phononic mode resonance and reveals the transmission properties of the phonons, which are related to the variance of the frequency of the electromagnetic field. Moreover, when one mechanical mode is driven, different mode resonant properties could be achieved on the transmission spectrum of phonons between the two mechanical modes. We believe that the current work provides significant results for the research of phononic devices.

13.
Arterioscler Thromb Vasc Biol ; 36(9): 1919-27, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27417579

RESUMO

OBJECTIVE: Pathological ocular neovascularization is a major cause of blindness. Increased dietary intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFA) reduces retinal neovascularization and choroidal neovascularization (CNV), but ω-3 LCPUFA metabolites of a major metabolizing pathway, cytochrome P450 oxidase (CYP) 2C, promote ocular pathological angiogenesis. We hypothesized that inhibition of CYP2C activity will add to the protective effects of ω-3 LCPUFA on neovascular eye diseases. APPROACH AND RESULTS: The mouse models of oxygen-induced retinopathy and laser-induced CNV were used to investigate pathological angiogenesis in the retina and choroid, respectively. The plasma levels of ω-3 LCPUFA metabolites of CYP2C were determined by mass spectroscopy. Aortic ring and choroidal explant sprouting assays were used to investigate the effects of CYP2C inhibition and ω-3 LCPUFA-derived CYP2C metabolic products on angiogenesis ex vivo. We found that inhibition of CYP2C activity by montelukast added to the protective effects of ω-3 LCPUFA on retinal neovascularization and CNV by 30% and 20%, respectively. In CYP2C8-overexpressing mice fed a ω-3 LCPUFA diet, montelukast suppressed retinal neovascularization and CNV by 36% and 39% and reduced the plasma levels of CYP2C8 products. Soluble epoxide hydrolase inhibition, which blocks breakdown and inactivation of CYP2C ω-3 LCPUFA-derived active metabolites, increased oxygen-induced retinopathy and CNV in vivo. Exposure to selected ω-3 LCPUFA metabolites of CYP2C significantly reversed the suppression of both angiogenesis ex vivo and endothelial cell functions in vitro by the CYP2C inhibitor montelukast. CONCLUSIONS: Inhibition of CYP2C activity adds to the protective effects of ω-3 LCPUFA on pathological retinal neovascularization and CNV.


Assuntos
Acetatos/farmacologia , Inibidores da Angiogênese/farmacologia , Neovascularização de Coroide/prevenção & controle , Inibidores do Citocromo P-450 CYP2C8/farmacologia , Citocromo P-450 CYP2C8/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Quinolinas/farmacologia , Neovascularização Retiniana/prevenção & controle , Retinopatia da Prematuridade/prevenção & controle , Animais , Aorta/efeitos dos fármacos , Aorta/enzimologia , Células Cultivadas , Neovascularização de Coroide/enzimologia , Neovascularização de Coroide/genética , Neovascularização de Coroide/fisiopatologia , Ciclopropanos , Citocromo P-450 CYP2C8/genética , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/enzimologia , Ácidos Graxos Ômega-3/metabolismo , Genótipo , Humanos , Hiperóxia/complicações , Lasers , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neovascularização Fisiológica/efeitos dos fármacos , Fenótipo , Neovascularização Retiniana/enzimologia , Neovascularização Retiniana/genética , Neovascularização Retiniana/fisiopatologia , Retinopatia da Prematuridade/enzimologia , Retinopatia da Prematuridade/genética , Retinopatia da Prematuridade/fisiopatologia , Sulfetos , Técnicas de Cultura de Tecidos
14.
Am J Physiol Heart Circ Physiol ; 311(3): H738-49, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27473938

RESUMO

Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in developed countries, and its prevalence will increase as the global incidence of diabetes grows exponentially. DR begins with an early nonproliferative stage in which retinal blood vessels and neurons degenerate as a consequence of chronic hyperglycemia, resulting in vasoregression and persistent retinal ischemia, metabolic disequilibrium, and inflammation. This is conducive to overcompensatory pathological neovascularization associated with advanced proliferative DR. Although DR is considered a microvascular complication, the retinal microvasculature is intimately associated with and governed by neurons and glia; neurodegeneration, neuroinflammation, and dysregulation of neurovascular cross talk are responsible in part for vascular abnormalities in both early nonproliferative DR and advanced proliferative DR. Neuronal activity directly regulates microvascular dilation and blood flow in the process of neurovascular coupling. Retinal neurons also secrete guidance cues in response to injury, ischemia, or metabolic stress that may either promote or suppress vascular outgrowth, either alleviating or exacerbating DR, contingent on the stage of disease and retinal microenvironment. Neurodegeneration, impaired neurovascular coupling, and dysregulation of neuronal guidance cues are key events in the pathogenesis of DR, and correcting these events may prevent or delay development of advanced DR. The review discusses the mechanisms of neurovascular cross talk and its dysregulation in DR, and their potential therapeutic implications.


Assuntos
Retinopatia Diabética/fisiopatologia , Isquemia/fisiopatologia , Neovascularização Patológica/fisiopatologia , Neuroglia/metabolismo , Acoplamento Neurovascular/fisiologia , Neurônios Retinianos/metabolismo , Vasos Retinianos/fisiopatologia , Estresse Fisiológico/fisiologia , Retinopatia Diabética/metabolismo , Proteínas do Olho/metabolismo , Humanos , Inflamação , Isquemia/metabolismo , Fatores de Crescimento Neural/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neuroglia/fisiologia , Fator de Crescimento Placentário/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Neurônios Retinianos/fisiologia , Vasos Retinianos/metabolismo , Semaforinas/metabolismo , Serpinas/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismo
15.
Arterioscler Thromb Vasc Biol ; 35(4): 855-64, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25657312

RESUMO

OBJECTIVE: The deficiency of very low-density lipoprotein receptor resulted in Wnt signaling activation and neovascularization in the retina. The present study sought to determine whether the very low-density lipoprotein receptor extracellular domain (VLN) is responsible for the inhibition of Wnt signaling in ocular tissues. APPROACH AND RESULTS: A plasmid expressing the soluble VLN was encapsulated with poly(lactide-co-glycolide acid) to form VLN nanoparticles (VLN-NP). Nanoparticles containing a plasmid expressing the low-density lipoprotein receptor extracellular domain nanoparticle were used as negative control. MTT, modified Boyden chamber, and Matrigel (™) assays were used to evaluate the inhibitory effect of VLN-NP on Wnt3a-stimulated endothelial cell proliferation, migration, and tube formation. Vldlr(-/-) mice, oxygen-induced retinopathy, and alkali burn-induced corneal neovascularization models were used to evaluate the effect of VLN-NP on ocular neovascularization. Wnt reporter mice (BAT-gal), Western blotting, and luciferase assay were used to evaluate Wnt pathway activity. Our results showed that VLN-NP specifically inhibited Wnt3a-induced endothelial cell proliferation, migration, and tube formation. Intravitreal injection of VLN-NP inhibited abnormal neovascularization in Vldlr(-/-), oxygen-induced retinopathy, and alkali burn-induced corneal neovascularization models, compared with low-density lipoprotein receptor extracellular domain nanoparticle. VLN-NP significantly inhibited the phosphorylation of low-density lipoprotein receptor-related protein 6, the accumulation of ß-catenin, and the expression of vascular endothelial growth factor in vivo and in vitro. CONCLUSIONS: Taken together, these results suggest that the soluble VLN is a negative regulator of the Wnt pathway and has antiangiogenic activities. Nanoparticle-mediated expression of VLN may thus represent a novel therapeutic approach to treat pathological ocular angiogenesis and potentially other vascular diseases affected by Wnt signaling.


Assuntos
Córnea/irrigação sanguínea , Neovascularização da Córnea/prevenção & controle , Ácido Láctico/química , Nanopartículas , Ácido Poliglicólico/química , Receptores de LDL/metabolismo , Neovascularização Retiniana/prevenção & controle , Vasos Retinianos/metabolismo , Transfecção/métodos , Via de Sinalização Wnt , Proteína Wnt3A/metabolismo , Animais , Movimento Celular , Proliferação de Células , Células Cultivadas , Neovascularização da Córnea/genética , Neovascularização da Córnea/metabolismo , Neovascularização da Córnea/fisiopatologia , Modelos Animais de Doenças , Humanos , Injeções Intravítreas , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Interferência de RNA , Ratos Sprague-Dawley , Receptores de LDL/genética , Neovascularização Retiniana/genética , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/fisiopatologia , Vasos Retinianos/fisiopatologia , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteína Wnt3A/genética , beta Catenina/metabolismo
16.
Int J Comput Assist Radiol Surg ; 19(6): 1175-1183, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38619792

RESUMO

PURPOSE: The internal carotid artery (ICA) is a region with a high incidence for small- and medium-sized saccular aneurysms. However, the treatment relies heavily on the surgeon's experience to achieve optimal outcome. Although the finite element method (FEM) and computational fluid dynamics can predict the postoperative outcomes, due to the computational complexity of traditional methods, there is an urgent need for investigating the fast but versatile approaches related to numerical simulations of flow diverters (FDs) deployment coupled with the hemodynamic analysis to determine the treatment plan. METHODS: We collected the preoperative and postoperative data from 34 patients (29 females, 5 males; mean age 55.74 ± 9.98 years) who were treated with a single flow diverter for small- to medium-sized intracranial saccular aneurysms on the ICA. The constraint-based virtual deployment (CVD) method is proposed to simulate the FDs expanding outward along the vessel centerline while be constrained by the inner wall of the vessel. RESULTS: The results indicate that there were no significant differences in the reduction rates of wall shear stress and aneurysms neck velocity between the FEM and methods. However, the solution time of CVD was greatly reduced by 98%. CONCLUSION: In the typical location of small- and medium-sized saccular aneurysms, namely the ICA, our virtual FDs deployment simulation effectively balances the computational accuracy and efficiency. Combined with hemodynamics analysis, our method can accurately represent the blood flow changes within the lesion region to assist surgeons in clinical decision-making.


Assuntos
Artéria Carótida Interna , Aneurisma Intracraniano , Humanos , Feminino , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/terapia , Masculino , Pessoa de Meia-Idade , Artéria Carótida Interna/cirurgia , Artéria Carótida Interna/fisiopatologia , Resultado do Tratamento , Hemodinâmica/fisiologia , Idoso , Análise de Elementos Finitos , Simulação por Computador , Stents , Angiografia Cerebral
17.
BMC Cell Biol ; 14: 8, 2013 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-23433118

RESUMO

BACKGROUND: The goal of this study was to investigate the anti-angiogenic activity of a novel peptide H-RN, derived from the hepatocyte growth factor kringle 1 domain (HGF K1), in a mouse model of corneal neovascularization. The anti-angiogenic effect of H-RN on vascular endothelial growth factor (VEGF)-stimulated cell proliferation, cell migration and endothelial cell tube formation was assessed in vitro using Human Umbilical Vein Endothelial Cells (HUVECs) and in vivo using a mouse cornea micropocket assay. Apoptosis and cell cycle arrest were assessed by flow cytometry. A scrambled peptide was used as a negative control. RESULTS: H-RN effectively inhibited VEGF-stimulated HUVEC proliferation, migration and tube formation on Matrigel, while a scrambled peptide exerted no effect. In the mouse model of corneal angiogenesis, VEGF-stimulated angiogenesis was significantly inhibited by H-RN compared to a scrambled peptide that had no such activity. VEGF protected HUVECs from apoptosis, while H-RN inhibited this protective effect of VEGF. VEGF significantly increased the proportion of cells in the S phase compared to control treated cells (p<0.05). Treatment with H-RN (1.5 mM) induced the accumulation of cells in G0/G1 phase, while the proportion of cells in the S phase and G2/M phase decreased significantly compared to control group (p<0.05). CONCLUSIONS: H-RN has anti-angiogenic activity in HUVECs and in a mouse model of VEGF-induced corneal neovascularization. The anti-angiogenic activity of H-RN was related to apoptosis and cell cycle arrest, indicating a potential strategy for anti-angiogenic treatment in the cornea.


Assuntos
Inibidores da Angiogênese/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Fator de Crescimento de Hepatócito/química , Fragmentos de Peptídeos/farmacologia , Inibidores da Angiogênese/uso terapêutico , Animais , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Colágeno/química , Córnea/irrigação sanguínea , Neovascularização da Córnea/tratamento farmacológico , Modelos Animais de Doenças , Combinação de Medicamentos , Fator de Crescimento de Hepatócito/farmacologia , Fator de Crescimento de Hepatócito/uso terapêutico , Células Endoteliais da Veia Umbilical Humana , Humanos , Laminina/química , Camundongos , Neovascularização Patológica , Fragmentos de Peptídeos/uso terapêutico , Estrutura Terciária de Proteína , Proteoglicanas/química , Fator A de Crescimento do Endotélio Vascular/farmacologia
18.
Materials (Basel) ; 16(20)2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37895666

RESUMO

The lifting operation of offshore pipelines is an important step in ocean pipeline engineering. An effective analytical method is developed for investigating the mechanical properties of the pipeline based on mechanical, physical, and geometric relationships. By using the shooting and the secant methods to transform the boundary value problem into an initial value one and then solving them with the Runge-Kutta method, the deformation and mechanical properties of the pipeline are calculated. Furthermore, based on the Det Norske Veritas (DNV) offshore standard, the mechanical properties of the pipeline are checked. The finite element method (FEM) by Orcaflex is employed to verify the accuracy of the analytical model. The effects of some factors such as the current velocity and lifting point position on the mechanical properties of the pipeline are analyzed based on the analytical model. The results indicate that the change in current velocity during the lifting process has a minimal effect on the pipeline, but the change in lifting point position significantly affects the deformation and mechanical properties of the pipeline.

19.
Cells ; 12(20)2023 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-37887287

RESUMO

Proper functioning of the neural retina relies on the unique retinal environment regulated by the blood-retinal barrier (BRB), which restricts the passage of solutes, fluids, and toxic substances. BRB impairment occurs in many retinal vascular diseases and the breakdown of BRB significantly contributes to disease pathology. Understanding the different molecular constituents and signaling pathways involved in BRB development and maintenance is therefore crucial in developing treatment modalities. This review summarizes the major molecular signaling pathways involved in inner BRB (iBRB) formation and maintenance, and representative animal models of eye diseases with retinal vascular leakage. Studies on Wnt/ß-catenin signaling are highlighted, which is critical for retinal and brain vascular angiogenesis and barriergenesis. Moreover, multiple in vivo and in vitro methods for the detection and analysis of vascular leakage are described, along with their advantages and limitations. These pre-clinical animal models and methods for assessing iBRB provide valuable experimental tools in delineating the molecular mechanisms of retinal vascular diseases and evaluating therapeutic drugs.


Assuntos
Doenças Retinianas , Doenças Vasculares , Animais , Barreira Hematorretiniana , Retina/metabolismo , Doenças Retinianas/metabolismo , Modelos Animais , Doenças Vasculares/metabolismo
20.
EJNMMI Res ; 13(1): 14, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36779997

RESUMO

OBJECTIVES: By comparing the prognostic performance of 18F-FDG PET/CT-based radiomics combining dose features [Includes Dosiomics feature and the dose volume histogram (DVH) features] with that of conventional radiomics in head and neck cancer (HNC), multidimensional prognostic models were constructed to investigate the overall survival (OS) in HNC. MATERIALS AND METHODS: A total of 220 cases from four centres based on the Cancer Imaging Archive public dataset were used in this study, 2260 radiomics features and 1116 dosiomics features and 8 DVH features were extracted for each case, and classified into seven different models of PET, CT, Dose, PET+CT, PET+Dose, CT+Dose and PET+CT+Dose. Features were selected by univariate Cox and Spearman correlation coefficients, and the selected features were brought into the least absolute shrinkage and selection operator (LASSO)-Cox model. A nomogram was constructed to visually analyse the prognostic impact of the incorporated dose features. C-index and Kaplan-Meier curves (log-rank analysis) were used to evaluate and compare these models. RESULTS: The cases from the four centres were divided into three different training and validation sets according to the hospitals. The PET+CT+Dose model had C-indexes of 0.873 (95% CI 0.812-0.934), 0.759 (95% CI 0.663-0.855) and 0.835 (95% CI 0.745-0.925) in the validation set respectively, outperforming the rest models overall. The PET+CT+Dose model did well in classifying patients into high- and low-risk groups under all three different sets of experiments (p < 0.05). CONCLUSION: Multidimensional model of radiomics features combining dosiomics features and DVH features showed high prognostic performance for predicting OS in patients with HNC.

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