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1.
Artigo em Inglês | MEDLINE | ID: mdl-34636536

RESUMO

Although organic artificial enzymes have been reported as biomimetic oxidation catalysts and are widely used for colorimetric biosensors, developing organic artificial enzymes with high enzymatic activity is still a challenge. Two-dimensional (2D) covalent organic frameworks (COFs) have shown superior potential in biocatalysts because of their periodic π-π arrays, tunable pore size and structure, large surface area, and thermal stability. The interconnection of electron acceptor and donor building blocks in the 2D conjugated COF skeleton can lead to narrower band gaps and efficient charge separation and transportation and thus is helpful to improve catalytic activity. Herein, a donor-acceptor 2D COF was synthesized using tetrakis(4-aminophenyl)pyrene (Py) as an electron donor and thieno[3,2-b]thiophene-2,5-dicarbaldehyde (TT) as an electron acceptor. Under visible light irradiation, the donor-acceptor 2D COF exhibited superior enzymatic catalytic activity, which could catalyze the oxidation of chromogenic substrates such as 3,3',5,5'-tetramethylbenzidine (TMB) by the formation of superoxide radicals and holes. Based on the above property, the photoactivated donor-acceptor 2D COF with enzyme-like catalytic properties was designed as a robust colorimetric probe for cheap, highly sensitive, and rapid colorimetric detection of glutathione (GSH); the corresponding linear range of GSH was 0.4-60 µM, and the limit of detection was 0.225 µM. This study not only presents the construction of COF-based light-activated nanozymes for environmentally friendly colorimetric detection of GSH but also provides a smart strategy for improving nanozyme activity.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34626114

RESUMO

Metformin, a clinical agent of type 2 diabetes, is reported as a potential geroprotector. Viral infection induces phenotypes of senescence in human T cells, and polyinosinic:polycytidylic acid (poly I:C), a viral mimic, induces upregulation of SA-ß-gal activity in ovary of the annual fish Nothobranchius guentheri. However, the effects and mechanisms of metformin on poly I:C-induced aging-like phenomena are poorly understood in vertebrates. In this study, the activity of SA-ß-gal increased in gut of 12-month-old fish and poly I:C-injected 6-month-old fish, compared to 6-month-old control fish, indicating that poly I:C induces aging-like phenomena in gut of the fish. Metformin supplementation retarded accumulation of SA-ß-gal in gut of old fish and poly I:C-treated young fish. The results of q-PCR analysis showed that metformin reduced NF-κB mediated inflammatory response including decreased level of pro-inflammatory cytokine IL-8 and increased expression of anti-inflammatory cytokine IL-10 in gut of the fish with natural aging and poly I:C-injected 6-month-old fish. Metformin also exhibited antioxidant effects, as it reduced ROS production which is associated with the upregulation of FoxO3a and PGC-1α in gut of 6-month-old fish with poly I:C-injection. Expression of AMPK and SIRT1 was reduced in gut of 6-month-old fish with poly I:C-treatment, and feeding metformin reversed these declines. Taken together, the present study suggested that poly I:C-injection led to aging-like phenomena in gut and metformin activated AMPK and SIRT1 to reduce NF-κB mediated inflammation and resist oxidative stress via enhanced expression of FoxO3a and PGC-1α, and finally delayed gut aging in vertebrates.

3.
Talanta ; 235: 122789, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517647

RESUMO

In this work, core-shell structured Ti4+-immobilized magnetic covalent organic frameworks (denoted as Fe3O4@TAPTDHTA-Ti4+ composites) were prepared for enhanced phosphopeptide enrichment by one-pot synthesis of COFs shell with inherent bifunctional groups on Fe3O4 NPs and further Ti4+ immobilization. The widely distributed bifunctional groups could provide abundant chelating sites for Ti4+ immobilizing. Combining with the high specific surface area and mesoporous structure, the Fe3O4@TAPTDHTA-Ti4+ composites exhibited excellent enrichment efficiency for phosphopeptides, such as low detection limit (0.05 fmol µL-1), high selectivity (1:5000 of molar ratio of ß-casein/bovine serum albumin (BSA) tryptic digests), high adsorption capacity (62.9 µg mg-1) and strong size-exclusive effect (1:250:250 of molar ratio of ß-casein tryptic digest/ß-casein/BSA). In addition, this method was general for immobilizing other metal ions (Zr4+ and Fe3+). Notably, the Fe3O4@TAPTDHTA-Fe3+ composites exhibited controllable affinity towards mono-phosphopeptides and multi-phosphopeptides. Furthermore, the Fe3O4@TAPTDHTA-Ti4+ composites were successfully applied to selectively capture phosphopeptides from complex biological samples including the tryptic digest of nonfat milk, human serum and human saliva. More significantly, 3333 phosphopeptides derived from 1409 phosphoproteins with 3492 phosphorylation sites were clearly identified from the tryptic digest of HeLa cell lysate. In addition to providing a potential excellent enrichment probe for comprehensive phosphoproteomic analysis, this study also offers a new perspective for the functionalization of COFs.


Assuntos
Estruturas Metalorgânicas , Fosfopeptídeos , Animais , Bovinos , Feminino , Células HeLa , Humanos , Fenômenos Magnéticos , Titânio
4.
Artigo em Inglês | MEDLINE | ID: mdl-34433181

RESUMO

The human aspartyl ß-hydroxylase (ASPH) is overexpressed in tumor tissues. Bronchoalveolar lavage (BAL) is a diagnostic procedure for infections and malignancies. The aim of this study was to investigate whether tumor exosomes carrying ASPH gene marker were present in bronchoalveolar fluid of patients with non-small cell lung cancer (NSCLC). A tissue microarray analysis was applied to explore the expression of ASPH in different histologic NSCLC. The human NSCLC cell lines and normal bronchial cell lines were used to study exosomal ASPH exprerssion. A total of 27 NSCLC, 21 benign tumor, and 15 healthy controls underwent BAL. Immunohistochemistry was performed to study the ASPH expression in malignant and normal lung tissues. The expression characteristics of ASPH in different NSCLC and normal bronchial cells and pneumocytes were confirmed by cell blocks. A reverse transcription-quantitative polymerase chain reaction was carried out to study the levels of exosomal ASPH expression. Immunohistochemical staining of tissue microarray demonstrated that overexpression of ASPH was found in NSCLC tissues including adenocarcinoma, large cell carcinoma, and squamous cell carcinoma, but absent in adjacent normal tissues. All NSCLC specimens exhibited high levels of ASPH immunoreactivity, while nonmalignant and normal lung tissues exhibited a very low level of expression. Overexpression of ASPH was found in exosomes from NSCLC cell lines but absent from the normal bronchial cell line NL-20. ASPH level from BAL exosomes was significantly increased in NSCLC patients compared with that from nonmalignant or health group. Our method of isolation of BAL exosomes was easily performed in the clinical laboratory. BAL exosomal ASPH can be a potential biomarker for NSCLC diagnosis.

5.
Chem Commun (Camb) ; 57(60): 7362-7365, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34196343

RESUMO

A facile strategy was introduced for room-temperature controllable synthesis of hierarchically flower-like hollow COFs (FHF-COFs). Furthermore, the universality for synthesis of the HFH-COFs was validated by altering the building units. Inspired by the unique morphology, extremely large surface area and good chemical stability, HFH-COFs could serve as an attractive adsorption probe by loading with gold nanoparticles and be applied to enrichment of brain natriuretic peptide from human serum. This work opens up a whole new approach for controllable synthesis of the HFH-COFs at room temperature and expands the application of COFs as a promising enrichment probe for complex biological samples.


Assuntos
Estruturas Metalorgânicas/química , Peptídeo Natriurético Encefálico/isolamento & purificação , Adsorção , Ouro/química , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Estruturas Metalorgânicas/síntese química , Peptídeo Natriurético Encefálico/sangue , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
6.
ACS Appl Mater Interfaces ; 13(28): 32823-32836, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34232612

RESUMO

Primary open-angle glaucoma is associated with elevated intraocular pressure (IOP) that damages the optic nerve and leads to gradual vision loss. Several agents that reduce the stiffness of pressure-regulating Schlemm's canal (SC) endothelial cells, in the conventional outflow pathway of the eye, lower IOP in glaucoma patients and are approved for clinical use. However, poor drug penetration and uncontrolled biodistribution limit their efficacy and produce local adverse effects. Compared to other ocular endothelia, FLT4/VEGFR3 is expressed at elevated levels by SC endothelial cells and can be exploited for targeted drug delivery. Here, we validate FLT4 receptors as clinically relevant targets on SC cells from glaucomatous human donors and engineer polymeric self-assembled nanocarriers displaying lipid-anchored targeting ligands that optimally engage this receptor. Targeting constructs were synthesized as lipid-PEGx-peptide, differing in the number of PEG spacer units (x), and were embedded in micelles. We present a novel proteolysis assay for quantifying ligand accessibility that we employ to design and optimize our FLT4-targeting strategy for glaucoma nanotherapy. Peptide accessibility to proteases correlated with receptor-mediated targeting enhancements. Increasing the accessibility of FLT4-binding peptides enhanced nanocarrier uptake by SC cells while simultaneously decreasing the uptake by off-target vascular endothelial cells. Using a paired longitudinal IOP study in vivo, we show that this enhanced targeting of SC cells translates to IOP reductions that are sustained for a significantly longer time as compared to controls. Confocal microscopy of murine anterior segment tissue confirmed nanocarrier localization to SC within 1 h after intracameral administration. This work demonstrates that steric effects between surface-displayed ligands and PEG coronas significantly impact the targeting performance of synthetic nanocarriers across multiple biological scales. Minimizing the obstruction of modular targeting ligands by PEG measurably improved the efficacy of glaucoma nanotherapy and is an important consideration for engineering PEGylated nanocarriers for targeted drug delivery.

7.
JMIR Res Protoc ; 10(7): e24423, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34283029

RESUMO

BACKGROUND: Approximately 70%-80% of kidney cancers are clear cell renal cell carcinomas (CCRCCs). Patient management is based on imaging (abdominal ultrasound and computerized tomography), surgical excision of the tumor, and pathological analysis. A tissue biopsy is therefore necessary to confirm the diagnosis and avoid unnecessary nephrectomy. For metastatic cancers, a tissue biopsy is essential for establishing the targeted therapy. This biopsy of tumor material is invasive and painful. Other techniques such as liquid biopsy would help reduce the need for tissue biopsy. The development of a simple biological test for diagnosis is essential. CA9 is a powerful marker for the diagnosis of CCRCC. Exosomes have become a major source of liquid biopsy because they carry tumor proteins, RNA, and lipids. Urine is the most convenient biological liquid for exosome sampling. OBJECTIVE: The aim of this study (PEP-C study) is mainly to determine whether it is possible to detect urinary exosomal CA9 for the molecular diagnosis of CCRCC. METHODS: This study will include 60 patients with CCRCC and 40 noncancer patients. Exosomes will be isolated from urine samples and exosomal CA9 will be detected by transmission electron microscopy, flow cytometry, and reverse transcription-quantitative polymerase chain reaction. RESULTS: This study is currently underway with funding support from the CHU Saint-Etienne of France. CONCLUSIONS: We expect to demonstrate that urinary tumor exosomes could be a novel liquid biopsy to diagnose CCRCC and to guide clinicians in treatment decision-making. TRIAL REGISTRATION: ClinicalTrials.gov NCT04053855; https://clinicaltrials.gov/ct2/show/NCT04053855. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24423.

8.
Int J Nanomedicine ; 16: 4805-4811, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285483

RESUMO

Objective: The objective of this study was to assess the possibility of using urinary exosomal CA9 mRNA as a novel liquid biopsy for the molecular diagnosis of bladder cancer. Patients and Methods: A total of 168 bladder cancer patients and 90 control subjects were included in the study. An isolation kit was used to isolate urinary exosomes. Transmission electron microscopy (TEM) was used to examine the presence of exosomes. Flow cytometry was used to examine the exosomal marker CD63. The expression level of exosomal CA9 mRNA was detected by RT-qPCR. The diagnostic performance of urinary urinary exosomal CA9 mRNA was evaluated. Results: TEM confirmed the enriched exosomes from urinary bladder patients. Flow cytometry indicated a strong positive expression of exosome marker CD63. Successful extraction of RNA was performed from exosome samples. The level of urinary exosomal CA9 mRNA was significantly higher in bladder cancer group than in control group (p<0.001). The area under the ROC curve was 0.837 (95% CI: 0.743-0.859) with a sensitivity of 85.18% and a specificity of 83.15% for the diagnosis of bladder cancer. Conclusion: We found that the urinary exosomes were abundant in the urine of bladder cancer patients. CA9 mRNA could be detectable in urinary exosomes. The urinary exosomal CA9 mRNA may present a new liquid biopsy for the diagnosis of bladder cancer.


Assuntos
Exossomos , Neoplasias da Bexiga Urinária , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias , Anidrase Carbônica IX , Feminino , Humanos , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Curva ROC , Neoplasias da Bexiga Urinária/diagnóstico
9.
Artigo em Inglês | MEDLINE | ID: mdl-34296860

RESUMO

The nonlinear response of a material to an external stimulus is vital in fundamental science and technical applications. The power-law current-voltage relationship of a varistor is one such example. An excellent example of such behavior is the power-law current-voltage relationship exhibited by Bi2O3-doped ZnO varistor ceramics, which are the cornerstone of commercial varistor materials for overvoltage protection. Here, we report on a sustainable, ZnO-based varistor ceramic, without the volatile Bi2O3, that is based on Cr2O3 as the varistor former and oxides of Ca, Co, and Sb as the performance enhancers. The material has an ultrahigh α of up to 219, a low IL of less than 0.2 µA/cm2, and a high Eb of up to 925 V/mm, making it superior to state-of-the-art varistor ceramics. The results provide insights into the design of materials with specific characteristics by tailoring states at the grain boundaries. The discovery of this ZnO-Cr2O3-type varistor ceramic represents a major breakthrough in the field of varistors for overvoltage protection and could drastically affect the world market for overvoltage protection.

10.
Analyst ; 146(9): 2991-2997, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33949450

RESUMO

A spherical thiol-functionalized covalent organic framework (COF-SH) was designed via a facile thiol-yne click reaction of a alkynyl-terminated COF and pentaerythritol tetra(3-mercaptopropionate). The COF-SH was explored as a new adsorbent for the selective enrichment of Hg2+. The as-prepared COF-SH exhibited a uniform mesoporous structure, a high abundance of binding sites, and good chemical stability, which endow it with great performance for the adsorption of Hg2+ and its corresponding maximum adsorption capacity was up to 617.3 mg g-1. Furthermore, the adsorption behavior of Hg2+ on the COF-SH wasin good agreement with the Langmuir and pseudo-second-order models. The influences of adsorbent dosage, pH, selectivity, and reusability of the COF-SH on Hg2+ adsorption were also investigated. Besides this, the COF-SH showed high selectivity towards Hg2+ even in the presence of a high concentration of K+, Na+, Ca2+, Mg2+ and Zn2+ metal ions. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), the corresponding limit of detection (LOD) of Hg2+ was determined at very low concentrations of 80 pg mL-1 (equal to 396 amoL µL-1). In addition, the COF-SH was successfully applied to rapidly enrich and sensitively detect Hg2+ in industrial sewage, with recoveries in the range of 101.8-103.4%, demonstrating the promising potential of COF-SH as an effective adsorbent for use in environmental sample pretreatment.

11.
Int J Biol Macromol ; 182: 264-275, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33836193

RESUMO

Deleted in liver cancer 1 (DLC1) is a recognized tumor suppressor gene that negatively regulates Rho family proteins by hydrolyzing the active GTP-bound state to its inactive GDP-bound state. Active Rho proteins play a positive role in tumorigenesis. Numerous in vitro and in vivo experiments have shown that DLC1 is downregulated or inactivated in various solid tumors, which may be due to the following five reasons: genomic deletion, epigenetic modification and ubiquitin-dependent proteasomal degradation may cause DLC1 underexpression; phosphorylation at the post-translation level may cause DLC1 inactivation; and failure to localize at focal adhesions (FAs) may prevent DLC1 from exerting full activity. All of the causes could be attributed to molecular binding. Experimental evidence suggests that direct or indirect targeting of DLC1 is feasible for cancer treatment. Therefore, elucidating the interaction of DLC1 with its binding partners might provide novel targeted therapies for cancer. In this review, we summarized the binding partners of DLC1 at both the gene and protein levels and expounded a variety of anticancer drugs targeting DLC1 to provide information about DLC1 as a cancer diagnostic indicator or therapeutic target.


Assuntos
Proteínas Ativadoras de GTPase/metabolismo , Neoplasias/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Transformação Celular Neoplásica/metabolismo , Proteínas Ativadoras de GTPase/antagonistas & inibidores , Proteínas Ativadoras de GTPase/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética
12.
Elife ; 102021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33783352

RESUMO

Glucocorticoids are widely used as an ophthalmic medication. A common, sight-threatening adverse event of glucocorticoid usage is ocular hypertension, caused by dysfunction of the conventional outflow pathway. We report that netarsudil, a rho-kinase inhibitor, decreased glucocorticoid-induced ocular hypertension in patients whose intraocular pressures were poorly controlled by standard medications. Mechanistic studies in our established mouse model of glucocorticoid-induced ocular hypertension show that netarsudil both prevented and reduced intraocular pressure elevation. Further, netarsudil attenuated characteristic steroid-induced pathologies as assessed by quantification of outflow function and tissue stiffness, and morphological and immunohistochemical indicators of tissue fibrosis. Thus, rho-kinase inhibitors act directly on conventional outflow cells to prevent or attenuate fibrotic disease processes in glucocorticoid-induced ocular hypertension in an immune-privileged environment. Moreover, these data motivate the need for a randomized prospective clinical study to determine whether netarsudil is indeed superior to first-line anti-glaucoma drugs in lowering steroid-induced ocular hypertension.


Assuntos
Anti-Hipertensivos/farmacologia , Benzoatos/farmacologia , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/tratamento farmacológico , beta-Alanina/análogos & derivados , Quinases Associadas a rho/antagonistas & inibidores , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Recém-Nascido , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Estudos Prospectivos , Tonometria Ocular , beta-Alanina/farmacologia
13.
J Alzheimers Dis ; 80(2): 539-553, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33579844

RESUMO

BACKGROUND: The World Alzheimer Report has described and predicted the economic burden of Alzheimer's disease (AD) patients in detail for four consecutive years. There was a large-scale national survey in China launched by Professor Jianping Jia in 2015, but it did not adequately represent the average economic burden of AD patients in Zhejiang Province. OBJECTIVE: To investigate the economic burden and main factors influencing Alzheimer's disease (AD) in Zhejiang Province. METHODS: We recruited 830 patients from 10 cities in Zhejiang Province, evaluated their per capita and total cost related to AD treatment and care in 2017, and analyzed the main factors affecting economic burden from the perspective of demographic characteristics and disease severity. RESULTS: In 2017, per capita cost of AD was 114,343.7 yuan, while the total cost was 27.53 billion yuan, accounting for 0.77% of Zhejiang Province's GDP (5176.8 billion yuan). Total cost, direct medical cost, and indirect cost have different correlations with age, education level, type of work, marital status, comorbidity, and disease severity. CONCLUSION: The economic burden of AD in Zhejiang Province is heavy, similar to the national burden, and interventions based on demographic characteristics and disease severity can help reduce it.


Assuntos
Doença de Alzheimer/economia , Efeitos Psicossociais da Doença , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China , Comorbidade , Escolaridade , Emprego , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Estado Civil , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Fatores Socioeconômicos , Inquéritos e Questionários
14.
Braz J Med Biol Res ; 54(4): e10370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33624731

RESUMO

This study aimed to investigate the effect of WeChat-based education and rehabilitation program (WERP) on anxiety, depression, health-related quality of life (HRQoL), major adverse cardiac/cerebrovascular events (MACCE)-free survival, and loss to follow-up rate in unprotected left main coronary artery disease (ULMCAD) patients after coronary artery bypass grafting (CABG). In this randomized controlled study, 140 ULMCAD patients who underwent CABG were randomly assigned to WERP group (n=70) or control care (CC) group (n=70). During the 12-month intervention period, anxiety and depression (using hospital anxiety and depression scale (HADS)) and HRQoL (using 12-Item Short-Form Health Survey (SF-12)) were assessed longitudinally. During the total 36-month follow-up period (12-month intervention and 24-month non-intervention periods), MACCE and loss to follow-up were recorded. During the intervention period, HADS-anxiety score at month 9 (M9) (P=0.047) and month 12 (M12) (P=0.034), anxiety rate at M12 (P=0.028), and HADS-D score at M12 (P=0.048) were all reduced in WERP group compared with CC group. As for HRQoL, SF-12 physical component summary score at M9 (P=0.020) and M12 (P=0.010) and SF-12 mental component summary score at M9 (P=0.040) and M12 (P=0.028) were all increased in WERP group compared with CC group. During the total follow-up period, WERP group displayed a trend of longer MACCE-free survival than that in CC group but without statistical significance (P=0.195). Additionally, loss to follow-up rate was attenuated in WERP group compared with CC group (P=0.033). WERP serves as an effective approach in optimizing mental health care and promoting life quality in ULMCAD patients after CABG.


Assuntos
Doença da Artéria Coronariana , Qualidade de Vida , Ansiedade/prevenção & controle , Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Depressão/prevenção & controle , Seguimentos , Humanos
15.
Molecules ; 26(4)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546294

RESUMO

Coumarins possesses immeasurable antitumor potential with minimum side effects depending on the substitutions on the basic nucleus, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, a series of coumarin sulfonamides and amides derivatives were designed and synthetized. The majority of these derivatives showed good cytotoxic activity against MDA-MB-231 and KB cell lines, among which compound 9c was the most potent against MDA-MB-231 cells, with IC50 value of 9.33 µM, comparable to 5-fluorouracil. Further investigation revealed that compound 9c had versatile properties against tumors, including inhibition of cell migration and invasion as well as inducing apoptosis. Reactive oxygen species (ROS) assay and western blotting analysis suggested that compound 9c promoted cancer cell apoptosis by increasing ROS levels and upregulating the expression of caspase-3 in MDA-MB-231 cells. These results indicated that compound 9c could be promising lead compound for further antitumor drug research.


Assuntos
Cumarínicos , Desenho de Fármacos , Neoplasias/tratamento farmacológico , Sulfonamidas , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Cumarínicos/síntese química , Cumarínicos/química , Cumarínicos/farmacologia , Células HCT116 , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Sulfonamidas/síntese química , Sulfonamidas/química , Sulfonamidas/farmacologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-33497334

RESUMO

Style transfer on images has achieved significant advances in recent years, with the deep convolutional neural network (CNN). Directly applying image style transfer algorithms to each frame of a video independently often leads to flickering and unstable results. In this work, we present a self-supervised space-time convolutional neural network (CNN) based method for online video style transfer, named as VTNet, which is end-to-end trained from nearly unlimited unlabeled video data to produce temporally coherent stylized videos in real-time. Specifically, our VTNet transfer the style of a reference image to the source video frames, which is formed by the temporal prediction branch and the stylizing branch. The temporal prediction branch is used to capture discriminative spatiotemporal features for temporal consistency, pretrained in an adversarial manner from unlabeled video data. The stylizing branch is used to transfer the style image to a video frame with the guidance from the temporal prediction branch to ensure temporal consistency. To guide the training of VTNet, we introduce the style-coherence loss net (SCNet), which assembles the content loss, the style loss, and the new designed coherence loss. These losses are computed based on high-level features extracted from a pretrained VGG-16 network. The content loss is used to preserve high-level abstract contents of the input frames, and the style loss introduces new colors and patterns from the style image. Instead of using optical flow to explicitly redress the stylized video frames, we design the coherence loss to make the stylized video inherit the dynamics and motion patterns from the source video to remove temporal flickering. Extensive subjective and objective evaluations on various styles demonstrate that the proposed method achieves favorable results against the state-of-the-arts with high efficiency.

17.
Exp Eye Res ; 202: 108374, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33253706

RESUMO

The iris plays an important role in certain types of glaucoma, including primary angle-closure glaucoma and pigmentary glaucoma. Iris mechanics are also important in influencing trabecular meshwork deformation in response to intraocular pressure changes in some animal species. Although mice are widely used to study ocular disease, including glaucoma, the in vivo biomechanical properties of the murine iris are unknown. Thus, the primary objective of this study was to estimate murine iris biomechanical stiffness. We used optical coherence tomography (OCT) images of the anterior segment of living mice (n = 13, age = 7.3 ± 3.2 [mean ± SD] months) at sequentially increasing IOP levels, observing IOP-dependent iris deformations. We then used an inverse finite element model to predict iris deformations under the same conditions, estimating iris stiffness by maximizing agreement between OCT data and numerical simulations. Our results show an in vivo murine iris stiffness of 96.1 ± 54.7 kPa (mean ± SD), which did not correlate with age but was dependent on gender. Our results further showed strong evidence of reverse pupillary block, with mean posterior chamber pressure remaining at approximately 12 mmHg even as anterior chamber pressure was set to much higher levels. Our approach to monitoring iris stiffness in vivo is applicable to study potential changes of iris stiffness in various pathophysiological conditions and thus has significant potential for clinical care of ocular disease involving iris biomechanics.


Assuntos
Glaucoma/fisiopatologia , Iris/fisiopatologia , Animais , Fenômenos Biomecânicos , Modelos Animais de Doenças , Feminino , Análise de Elementos Finitos , Glaucoma/diagnóstico , Gonioscopia , Pressão Intraocular , Iris/diagnóstico por imagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tomografia de Coerência Óptica/métodos
18.
Braz. j. med. biol. res ; 54(4): e10370, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1153538

RESUMO

This study aimed to investigate the effect of WeChat-based education and rehabilitation program (WERP) on anxiety, depression, health-related quality of life (HRQoL), major adverse cardiac/cerebrovascular events (MACCE)-free survival, and loss to follow-up rate in unprotected left main coronary artery disease (ULMCAD) patients after coronary artery bypass grafting (CABG). In this randomized controlled study, 140 ULMCAD patients who underwent CABG were randomly assigned to WERP group (n=70) or control care (CC) group (n=70). During the 12-month intervention period, anxiety and depression (using hospital anxiety and depression scale (HADS)) and HRQoL (using 12-Item Short-Form Health Survey (SF-12)) were assessed longitudinally. During the total 36-month follow-up period (12-month intervention and 24-month non-intervention periods), MACCE and loss to follow-up were recorded. During the intervention period, HADS-anxiety score at month 9 (M9) (P=0.047) and month 12 (M12) (P=0.034), anxiety rate at M12 (P=0.028), and HADS-D score at M12 (P=0.048) were all reduced in WERP group compared with CC group. As for HRQoL, SF-12 physical component summary score at M9 (P=0.020) and M12 (P=0.010) and SF-12 mental component summary score at M9 (P=0.040) and M12 (P=0.028) were all increased in WERP group compared with CC group. During the total follow-up period, WERP group displayed a trend of longer MACCE-free survival than that in CC group but without statistical significance (P=0.195). Additionally, loss to follow-up rate was attenuated in WERP group compared with CC group (P=0.033). WERP serves as an effective approach in optimizing mental health care and promoting life quality in ULMCAD patients after CABG.


Assuntos
Humanos , Qualidade de Vida , Doença da Artéria Coronariana/cirurgia , Ansiedade/prevenção & controle , Ponte de Artéria Coronária , Seguimentos , Depressão/prevenção & controle
19.
Artigo em Inglês | MEDLINE | ID: mdl-33315562

RESUMO

The crowd counting is challenging for deep networks due to several factors. For instance, the networks can not efficiently analyze the perspective information of arbitrary scenes, and they are naturally inefficient to handle the scale variations. In this work, we deliver a simple yet efficient multi-column network, which integrates the perspective analysis method with the counting network. The proposed method explicitly excavates the perspective information and drives the counting network to analyze the scenes. More concretely, we explore the perspective information from the estimated density maps and quantify the perspective space into several separate scenes. We then embed the perspective analysis into the multi-column framework with a recurrent connection. Therefore, the proposed network matches various scales with the different receptive fields efficiently. Secondly, we share the parameters of the branches with various receptive fields. This strategy drives the convolutional kernels to be sensitive to the instances with various scales. Furthermore, to improve the evaluation accuracy of the column with a large receptive field, we propose a transform dilated convolution. The transform dilated convolution breaks the fixed sampling structure of the deep network. Moreover, it needs no extra parameters and training, and the offsets are constrained in a local region, which is designed for the congested scenes. The proposed method achieves state-of-the-art performance on five datasets (ShanghaiTech, UCF CC 50, WorldEXPO10, UCSD, and TRANCOS).

20.
Invest Ophthalmol Vis Sci ; 61(14): 12, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315051

RESUMO

Purpose: Tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) activation in Schlemm's canal (SC) endothelium is required for the maintenance of IOP, making the angiopoietin/Tie2 pathway a target for new and potentially disease modifying glaucoma therapies. The goal of the present study was to examine the effects of a Tie2 activator, AKB-9778, on IOP and outflow function. Methods: AKB-9778 effects on IOP was evaluated in humans, rabbits, and mice. Localization studies of vascular endothelial protein tyrosine phosphatase (VE-PTP), the target of AKB-9778 and a negative regulator of Tie2, were performed in human and mouse eyes. Mechanistic studies were carried out in mice, monitoring AKB-9778 effects on outflow facility, Tie2 phosphorylation, and filtration area of SC. Results: AKB-9778 lowered IOP in patients treated subcutaneously for diabetic eye disease. In addition to efficacious, dose-dependent IOP lowering in rabbit eyes, topical ocular AKB-9778 increased Tie2 activation in SC endothelium, reduced IOP, and increased outflow facility in mouse eyes. VE-PTP was localized to SC endothelial cells in human and mouse eyes. Mechanistically, AKB-9778 increased the filtration area of SC for aqueous humor efflux in both wild type and in Tie2+/- mice. Conclusions: This is the first report of IOP lowering in humans with a Tie2 activator and functional demonstration of its action in remodeling SC to increase outflow facility and lower IOP in fully developed mice. Based on these studies, a phase II clinical trial is in progress to advance topical ocular AKB-9778 as a first in class, Tie2 activator for treatment for ocular hypertension and glaucoma.


Assuntos
Compostos de Anilina/farmacologia , Pressão Intraocular/efeitos dos fármacos , Receptor TIE-2/metabolismo , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/antagonistas & inibidores , Ácidos Sulfônicos/farmacologia , Malha Trabecular/efeitos dos fármacos , Animais , Retinopatia Diabética/tratamento farmacológico , Método Duplo-Cego , Feminino , Imunofluorescência , Glaucoma/tratamento farmacológico , Glaucoma/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Malha Trabecular/metabolismo , Malha Trabecular/patologia
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