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1.
Artigo em Inglês | MEDLINE | ID: mdl-33621178

RESUMO

We propose a new video vectorization approach for converting videos in the raster format to vector representation with the benefits of resolution independence and compact storage. Through classifying extracted curves on each video frame as salient ones and non-salient ones, we introduce a novel bipartite diffusion curves (BDCs) representation in order to preserve both important image features such as sharp boundaries and regions with smooth color variation. This bipartite representation allows us to propagate non-salient curves across frames such that the propagation in conjunction with geometry optimization and color optimization of salient curves ensures the preservation of fine details within each frame and across different frames, and meanwhile, achieves good spatial-temporal coherence. Thorough experiments on a variety of videos show that our method is capable of converting videos to the vector representation with low reconstruction errors, low computational cost and fine details, demonstrating our superior performance over the state-of-the-arts. Our approach can also produce comparable results to video super-resolution.

2.
Chem Biol Drug Des ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33245189

RESUMO

Cisplatin has strong broad-spectrum anticancer activity and is one of the most effective anticancer drugs currently used. The clinical application of cisplatin has led to the resistance of cancer cells to cisplatin. Tachyplesin is an active, natural marine peptide with antitumour activity. In the present study, we investigated whether tachyplesin can be used in non-small cell lung cancer (NSCLC) A549 and H460 cells as well as the cisplatin-resistant human A549/DDP NSCLC cell line. The results revealed that tachyplesin treatment significantly inhibited proliferation and induced apoptosis in A549 and H460 cells and the combination of tachyplesin and cisplatin significantly suppressed migration and improved sensitivity to cisplatin in A549/DDP cells. Further mechanistic examination revealed that tachyplesin induced apoptosis in A549/DDP cells by increasing Fas, FasL and p-RIPK1 levels. These results indicated that tachyplesin induces lung cancer death by activating the Fas, mitochondrial and necroptosis pathways. Tachyplesin could be developed as a candidate drug for cisplatin-resistant NSCLC.

4.
Gastrointest Endosc ; 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32522483

RESUMO

BACKGROUND AND AIMS: Heller myotomy (HM) is considered the standard surgical treatment for patients with achalasia. However, approximately 10% to 20% of patients with achalasia have persistent or recurrent symptoms after HM that require further therapy. Several studies have reported the outcomes of peroral endoscopic myotomy (POEM) in these patients. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of POEM in patients with achalasia with previous HM. METHODS: An electronic literature search of PubMed, Embase, and the Cochrane Library was conducted up to January 31, 2020. Studies evaluating the outcomes of POEM in patients with achalasia with previous HM were eligible for inclusion. The primary outcomes were the pooled rates of clinical success (defined as post-POEM Eckardt score ≤3), mean change in Eckardt score, lower esophageal sphincter pressure, and integrated relaxation pressure (IRP). The secondary outcomes were procedure-related adverse events (AEs) and incidence of postoperative GERD. RESULTS: A total of 9 studies involving 272 patients with achalasia were recruited in this review. POEM was successfully performed in 270 (99.3%) patients after previous HM. Clinical success was achieved in 90.0% (95% confidence interval [CI], 83.1%-96.8%) of patients. Eckardt score, lower esophageal sphincter pressure, and IRP were significantly lowered by 5.14 (95% CI, 4.19-6.09), 12.01 mm Hg (95% CI, 6.74-17.27), and 10.02 mm Hg (95% CI, 4.95-15.09), respectively. The pooled rates of postoperative symptomatic reflux, esophagitis, and abnormal pH monitoring were 36.9% (95% CI, 20.7%-53.1%), 33.0% (95% CI, 9.6%-56.4%), and 47.8% (95% CI, 33.4%-62.2%), respectively. Substantial heterogeneity was detected across all outcome measurements. Most of the AEs were self-limiting or managed conservatively. CONCLUSIONS: POEM is a safe and effective treatment for patients with achalasia with previous HM. Further data from prospective, controlled studies with long-term follow-up are needed to confirm these findings.

5.
Soft Matter ; 16(18): 4540-4548, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32356540

RESUMO

Native tissues such as nerve bundles, blood vessels and tendons have extracellular matrices with a characteristic linear orientation, which cannot be fully achieved with the current technology for the development of regenerative biomaterials. In this study, bioactive and oriented collagen filaments have been fabricated using a combination of wet-spinning and carbodiimide-based crosslinking. The wet-spinning techniques, including extrusion and collection rates, and their influences on collagen filaments were studied and optimized. The diameter of the attained collagen filaments can be adjusted ranging from 30 µm to 650 µm. Further characterizations, such as circular dichroism, scanning electron microscopy, small-angle X-ray scattering and Fourier transform infrared spectra analysis, showed that the native structure of the collagen was greatly preserved after the filament preparation process. The measurements of weight swelling ratio and degradation rate indicate that the crosslinking method can efficiently regulate the physico-chemical properties of collagen filaments, including water absorption and degradation behaviors. In particular, the mechanical strength of collagen filaments can be greatly improved via crosslinking. In addition, cells can adhere and spread on collagen filaments in well-aligned patterns, showing appropriate biological features. It can be concluded that the bioactive collagen filaments with tunable properties are preferable for developing tissue engineering scaffolds with characteristic orientation features. With further study of the interactions between collagen filaments and cells, this work may shed light on the development of collagen based biomaterials that would be beneficial in the field of tissue engineering.

7.
Acta Biomater ; 91: 159-172, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31055122

RESUMO

Hydrogels, which provide three-dimensional (3D) niches for encapsulating bone marrow mesenchymal stem cells (BMSCs), are becoming a promising tissue engineering solution for chondrogenic differentiation of BMSCs. However, it remains a challenge to design a hydrogel material for effective chondrogenesis of BMSCs because of the complexity of cartilage ECM and cell-matrix interactions. Thus far, various studies have shown the physical-chemical cues of hydrogel materials to impact BMSCs chondrogenesis, but the design of the 3D network microstructure of the hydrogel to induce BMSCs chondrogenesis is still far from optimized. In this study, we successfully prepared two types of collagen hydrogels, namely, the fibrous network and porous network, with the same chemical composition and similar mechanical strength but with two distinct network microstructures. The two different network microstructures significantly influenced mass transfer, protein adsorption, degradability, and contraction of the collagen hydrogels. Moreover, the cells presented distinct proliferation and morphology in the two hydrogels, which consequently modulated chondrogenic differentiation of BMSCs derived from rat. Collagen hydrogels with a fibrous network promoted more chondrogenic differentiation of BMSCs without additional growth factors in vitro and subcutaneous implantation in vivo than those with a porous network. Moreover, fibrous network resulted in less ECM calcification than porous network. However, the fibrous network could not prevent hypertrophy of the chondrogenic cells induced by BMSCs. Overall, these results revealed that the 3D network microstructure of a hydrogel was a key design parameter for the chondrogenic differentiation of BMSCs. STATEMENT OF SIGNIFICANCE: Hydrogels had been used to induce the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in cartilage tissue engineering, but the key design parameters remain unoptimized. This was mainly due to the different material properties including composition, strength, and microstructure, which would interplay with each other and result in difficulties to investigate the effects for one factor. In this study, we fabricated two collagen hydrogels with the same chemical composition and mechanical strength, but two distinct network microstructures. The effects of the two network microstructures on the chondrogenic differentiation of BMSCs were investigated by in vitro and in vivo assays. The results highlight the effects of network microstructures and provide important information about optimizing the design of future hydrogels in cartilage tissue engineering.


Assuntos
Condrogênese/efeitos dos fármacos , Colágeno , Matriz Extracelular/metabolismo , Hidrogéis , Células-Tronco Mesenquimais/metabolismo , Animais , Colágeno/química , Colágeno/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/citologia , Ratos
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2019: 3919-3922, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31946729

RESUMO

Laser speckle contrast imaging (LSCI) is a high-resolution full-field optical technique for measuring blood flow, which has been widely used in clinical and biomedical research. However, most of the current LSCI instruments are bulky, limiting their application settings. In this work, we proposed a prototype system of portable laser speckle imager. Different from the desktop laser speckle systems that utilize personal computer (PC), our system was designed with embedded GPU system (Jetson TX2, NVIDIA, USA) and a LCD touch screen (16.5 × 12.4 cm in size, 380 g in weight). In-vivo experiments showed that the portable GPU-based system had comparable performance with our laboratory LSCI system. Such a portable LSCI imager could be potentially used in a situation that requires for easy operation and installation, such as intraoperative monitoring or bedside diagnosis.


Assuntos
Gráficos por Computador , Hemodinâmica , Fluxometria por Laser-Doppler/instrumentação , Lasers , Humanos
9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2018: 21-24, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30440331

RESUMO

Brain plasticity after amputation is related to the short-term unmasking of latent synapses as well as the long-term reorganization due to the sprouting new synaptic connections. The cortical functional reorganization has been reported along the intact somatosensory pathway after unilateral deafferentation. Cerebral blood flow (CBF) change serves as an important biomarker of the functional reorganization of brain. Using laser speckle contrast imaging (LSCI) technology, we performed a longitudinal study to unveil the cortical functional reorganization after forelimb amputation in rodent model, particularly along the intact somatosensory pathway. Our results showed that the CBF response to electrical stimulation of the intact forepaw increased significantly at 9 hours after amputation in acute stage. While in chronic stage (>14 days), the CBF response showed a pattern similar to the control group. The results showed the dynamic brain functional response along the intact somatosensory pathway at different stages after amputation and indicated that cortical functional reorganization occurred within the acute stage. Our work provided additional insights in understanding the inter-hemispheric functional changes from acute to chronic stages of amputation.


Assuntos
Amputação , Membro Anterior , Plasticidade Neuronal , Córtex Somatossensorial , Animais , Estimulação Elétrica , Membro Anterior/fisiologia , Estudos Longitudinais , Plasticidade Neuronal/fisiologia , Roedores , Córtex Somatossensorial/fisiologia
10.
J Immunol Res ; 2018: 3673295, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30406152

RESUMO

Tumor is the most serious threat to human beings. Although war against cancer has been launched over forty years, cancer treatment is still far away from being satisfactory. Immunotherapy, especially checkpoint blockade immunotherapy, is a rising star that shows a promising future. To fulfill the requirement of depleting primary tumor and inhibiting tumor metastasis and recurrence, many researchers combined checkpoint blockade immunotherapy with other treatment strategies to extend the treatment outcome. Photodynamic therapy could induce immunogenic cell death, and checkpoint blockade could further accelerate the immunity; therefore, combining these two strategies publishes many papers. Additionally, photothermal therapy and immunotherapy were also utilized for combining with checkpoint blockade, which were also reviewed in this paper. Furthermore, antibodies, siRNA, and small molecule inhibitors are developed to block the checkpoint; therefore, we categorized the papers into three sections, combination nanoparticles with checkpoint blockade antibody, combination nanoparticles with checkpoint blockade siRNA, and combination nanoparticles with small molecule checkpoint inhibitors, and related researches were summarized. In conclusion, the combination nanoparticle with checkpoint blockade cancer immunity is a promising direction that may fulfill the requirement of cancer treatment.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Receptores Coestimuladores e Inibidores de Linfócitos T/metabolismo , Imunoterapia/métodos , Nanopartículas , Neoplasias/terapia , RNA Interferente Pequeno/uso terapêutico , Animais , Terapia Combinada , Receptores Coestimuladores e Inibidores de Linfócitos T/imunologia , Sistemas de Liberação de Medicamentos , Humanos , Neoplasias/imunologia , Fototerapia
11.
Ultrason Sonochem ; 48: 424-431, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30080569

RESUMO

This paper explores the mass transfer mechanism of microvias electroforming under ultrasonic agitation by numerical simulations and electrochemical experiments. Firstly, the velocity distribution of electroforming solution inside the microvias under ultrasound treatment is simulated by COMSOL Multiphysics software. The ultrasonic frequency is that of 120 kHz. The ultrasonic powers are 100 W, 200 W, 300 W and 400 W, respectively. The simulation results indicate that the mean liquid velocity inside the microvias increases with the increasing of acoustic power. In addition, under a certain ultrasonic power, the mean liquid velocity will decrease with increasing the distance between microvias and transducer, the aspect ratio of microvias and the distance between cathode and central position. Secondly, electrochemical experiments are presented to investigate the effect of ultrasonic agitation on the electrode kinetics of microvias electroforming. It is found that ultrasonic treatment decreases the thickness of diffusion layer, increases the limiting diffusion current densities and further enhances the mass transfer of microvias electroforming. Compared with the silent condition, the diffusion layer thicknesses with the acoustic power of 100 W, 200 W, 300 W, 400 W are decreased by 50.0%, 64.1%, 69.3% and 74.5%, respectively. Finally, according to the results above, the 200 × 200 metal micro-column array structures are fabricated by ultrasonic electroforming under the condition of 120 kHz and 200 W. The metal micro-column is 250 µm high and has a diameter of 80 µm. The results show that ultrasonic electroforming can enhance the mass transfer of microvias electroforming, and further solve the problem of porous structure in electroforming layer. This work contributes to expanding the application of ultrasonic agitation in the microvias electroforming.

12.
Biomed Res Int ; 2014: 364316, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25386559

RESUMO

Lung cancer is the leading cause of cancer-related death and cigarette smoking is the main risk factor for lung cancer. Circulating microRNAs (miRNAs) are considered potential biomarkers of various cancers, including lung cancer. However, it is unclear whether changes in circulating miRNAs are associated with smoking and smoking-related lung cancer. In this study, we determined the serum miRNA profiles of 10 nonsmokers, 10 smokers, and 10 lung-cancer patients with miRCURY LNA microRNA arrays. The differentially expressed miRNAs were then confirmed in a larger sample. We found that let-7i-3p and miR-154-5p were significantly downregulated in the sera of smokers and lung-cancer patients, so the serum levels of let-7i-3p and miR-154-5p are associated with smoking and smoking-related lung cancer. The areas under receiver operating characteristic curves for let-7i-3p and miR-154-5p were approximately 0.892 and 0.957, respectively. In conclusion, our results indicate that changes in serum miRNAs are associated with cigarette smoking and lung cancer and that let-7i-3p and miR-154-5p are potential biomarkers of smoking-related lung cancer.


Assuntos
Neoplasias Pulmonares/genética , MicroRNAs/biossíntese , Fumar/genética , Adulto , Idoso , Biomarcadores Tumorais/sangue , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/sangue , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Prognóstico , Fumar/efeitos adversos , Fumar/sangue
13.
Int J Clin Pharmacol Ther ; 52(6): 497-503, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24691060

RESUMO

OBJECTIVE: The purpose of this study was to investigate the associations between CYP3A4*18B and CYP3A5*3 polymorphism and cyclosporine-related liver injuries in Chinese renal transplant recipients. METHODS: We genotyped 339 renal transplant recipients treated with a triple immunosuppressive regimen including cyclosporine for CYP3A4*18B and CYP3A5*3 polymorphism using the polymerase chain reaction restriction fragment length polymorphism assay. RESULTS: The incidence of liver injury in the study population was 36.9% (125/339). At 1 month after transplantation, the trough concentration of cyclosporine (C0) in the group with CYP3A4*1/*1(GG alleles) was significantly higher than in the group with CYP3A4*18B/*1 8B(AA alleles) (p < 0.05). At 3 months after transplantation, the C0 in the group with CYP3A4*1/*1 and group with CYP3A4*1/*18B was markedly higher than in the group with CYP3A4*18B/*18B (p < 0.05). The GG genotypes of CYP3A4*18B were more common in the liver injury group compared with the control group (p < 0.05). Univariate logistic regression analysis showed that subjects carrying the GG genotypes had a 5.136- and 2.528-fold higher risk of developing cyclosporine-related liver injury than those with the AA and GA genotypes. When adjusted for sex, the risk of the CYP3A4*18B genotypes was OR = 4.969 for GG compared to AA (p = 0.030), and OR = 2.634 for GG compared to GA (p = 0.025). However, no association was observed between CYP3A5*3 polymorphisms with cyclosporine-related liver injury. CONCLUSIONS: These results suggested that the wild type of CYP3A4*18B is a risk factor for the development of cyclosporine- related liver injuries in Chinese renal transplant recipients.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ciclosporina/efeitos adversos , Citocromo P-450 CYP3A/genética , Imunossupressores/efeitos adversos , Transplante de Rim , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/etnologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Distribuição de Qui-Quadrado , China/epidemiologia , Ciclosporina/sangue , Citocromo P-450 CYP3A/metabolismo , Quimioterapia Combinada , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Imunossupressores/sangue , Incidência , Transplante de Rim/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Fatores de Risco , Fatores de Tempo , Adulto Jovem
14.
ScientificWorldJournal ; 2013: 396936, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24082851

RESUMO

Gable roof buildings are widely used in industrial buildings. Based on wind tunnel tests with rigid models, wind pressure distributions on gable roof buildings with different aspect ratios were measured simultaneously. Some characteristics of the measured wind pressure field on the surfaces of the models were analyzed, including mean wind pressure, fluctuating wind pressure, peak negative wind pressure, and characteristics of proper orthogonal decomposition results of the measured wind pressure field. The results show that extremely high local suctions often occur in the leading edges of longitudinal wall and windward roof, roof corner, and roof ridge which are the severe damaged locations under strong wind. The aspect ratio of building has a certain effect on the mean wind pressure coefficients, and the effect relates to wind attack angle. Compared with experimental results, the region division of roof corner and roof ridge from AIJ2004 is more reasonable than those from CECS102:2002 and MBMA2006.The contributions of the first several eigenvectors to the overall wind pressure distributions become much bigger. The investigation can offer some basic understanding for estimating wind load distribution on gable roof buildings and facilitate wind-resistant design of cladding components and their connections considering wind load path.


Assuntos
Modelos Teóricos , Pressão , Vento , Monitoramento Ambiental , Arquitetura de Instituições de Saúde
15.
Toxicol Sci ; 135(1): 63-71, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23761296

RESUMO

MicroRNAs (miRNAs) are small RNA molecules that regulate posttranscriptional gene expression. Previous research has suggested that aberrant miRNA expression often plays a critical role in many types of cancer, including lung cancer. However, the exact miRNAs that are involved in pulmonary carcinogenesis remain unclear. We investigated the miRNA-based molecular changes that occur in urethane-induced carcinogenicity and identified specific miRNA deregulation in pulmonary carcinogenesis induced by urethane. In this study, we used a lung cancer model in which Balb/c mice were exposed to urethane via ip injection once a week for four consecutive weeks. The mice were then killed in weeks 6, 12, or 24. Two small RNA libraries were constructed with the total RNA from the lung tumor and normal adjacent lung tissues of the urethane-injected mice collected in week 24. Using Solexa sequencing, we identified a plethora of differentially expressed miRNAs and predicted nine novel miRNAs. Further analysis demonstrated the sustainable downregulation of miR-1a in the lung tissues in lung carcinogenesis induced by urethane. The levels of miR-1a were also reduced in the serum. Our findings indicate that urethane exposure alters the expression of a cluster of miRNAs. The simultaneous downregulation of miR-1a in lung tissues and serum in urethane-induced pulmonary carcinogenesis suggests that miR-1a is associated with tumorigenesis.


Assuntos
Neoplasias Pulmonares/genética , MicroRNAs/análise , Transcriptoma , Animais , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/induzido quimicamente , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/sangue , MicroRNAs/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Uretana/toxicidade
16.
Toxicol Appl Pharmacol ; 267(3): 238-46, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23337359

RESUMO

The alteration of microRNA (miRNA) expression plays an important role in chemical carcinogenesis. Presently, few reports have been published that concern the significance of circulating miRNAs in lung carcinogenesis induced by environmental carcinogens. The purpose of this study was to identify serum miRNAs that could be associated with lung carcinogenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Male F344 rats were systemically administered with NNK. The rat serum differential expression profiles of miRNAs were analyzed by small RNA solexa sequencing. Using quantitative real-time PCR, the differentially expressed serum miRNAs were identified in each individual rat. Serum miR-206 and miR-133b were selected for further identification in rat serum at different stages of lung carcinogenesis; we detected the levels of serum miR-206 and miR-133b in lung cancer tissues induced by NNK. NNK causes significant alteration of serum miRNA expression. Compared to the control group, serum miR-206 and miR-133b were significantly up-regulated in the early stage of NNK-induced lung carcinogenesis. miR-206 and miR-133b exhibited low-expression in lung cancer tissues. Our results demonstrate that lung carcinogen NNK exposure changes the expression of serum miRNAs. Serum miR-206 and miR-133b could be associated with lung carcinogenesis induced by NNK.


Assuntos
Biomarcadores Tumorais/sangue , Carcinógenos/toxicidade , Neoplasias Pulmonares/sangue , MicroRNAs/sangue , Nitrosaminas/toxicidade , Animais , Biomarcadores Tumorais/genética , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Masculino , MicroRNAs/genética , Ratos , Ratos Endogâmicos F344 , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
17.
Carcinogenesis ; 33(1): 131-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22016468

RESUMO

Aberrant expression of microRNA (miRNA) has been previously demonstrated to play an important role in a wide range of cancer types and further elucidation of its role in the mechanisms underlying tumorigenesis, anticarcinogenesis and potential chemotherapeutics is warranted. We chose the anti-benzo[a]pyrene-7,8-diol-9,10-epoxide-transformed human bronchial epithelial cell line 16HBE-T to study miRNAs involved in anticarcinogenesis. In resveratrol-treated cells, we found that miR-622 was upregulated, whereas it was downregulated in 16HBE-T cells, suggesting that miR-622 potentially acts as a tumor suppressor. Increasing the level of miR-622 by transient transfection-induced inhibition of proliferation and G(0) arrest in 16HBE-T cells and the lung cancer cell line H460 as demonstrated by cell viability and cell cycle analysis. MiR-622 dramatically suppressed the ability of 16HBE-T cells to form colonies in vitro and to develop tumors in nude mice. According to bioinformatics analysis, K-Ras messenger RNA was predicted as a putative miR-622 target; this was confirmed by western blot and luciferase reporter assays. Cell growth retardation was inhibited upon knockdown of K-Ras and an increase in the level of miR-622 in 16HBE-T cells. Furthermore, miR-622 inhibitor partially impaired the growth of 16HBE-T cells as demonstrated by luciferase reporter activity and K-Ras protein expression in 16HBE-T cells. In summary, miR-622 functions as a tumor suppressor by targeting K-Ras and impacting the anticancer effect of resveratrol. Therefore, miR-622 is potentially useful as a clinical therapy. MiR-622 impacts the K-Ras signal pathway and the potentially anticarcinogenic or chemotherapeutic properties warrant further investigation.


Assuntos
Anticarcinógenos/farmacologia , Genes Supressores de Tumor/fisiologia , MicroRNAs/fisiologia , Proteínas Proto-Oncogênicas/genética , Estilbenos/farmacologia , Proteínas ras/genética , Animais , Brônquios/patologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Neoplasias Pulmonares/terapia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas p21(ras) , Resveratrol
18.
Toxicol Lett ; 205(3): 320-6, 2011 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-21726609

RESUMO

Growing evidence indicates that the alteration of microRNA (miRNA) expression in tumors that is induced by chemical carcinogens plays an important role in tumor development and progression. However, the mechanism underlying miRNA involvement in lung carcinogenesis induced by anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide (anti-BPDE) remains unclear. In our study, we used the malignant transformation of human bronchial epithelial cells (16HBE-T) induced by anti-BPDE to explore the mechanisms of human lung carcinogenesis. We found that expression of miR-506 was reduced in 16HBE-T transformed malignant human bronchial epithelial cells compared with 16HBE normal human bronchial epithelial cells. Restoration of miR-506 in 16HBE-T cells led to a decrease in cell proliferation, G0/G1 phase cell cycle arrest, as well as significantly suppressed anchorage-dependent growth in vitro and tumor growth inhibition in a nude mouse xenograft model. In addition, we provided novel evidence regarding the role miR-506 potentially plays in negatively regulating the protein and mRNA expression level of N-Ras in cancer cells. Together, these findings revealed that miR-506 acts as an anti-oncogenic miRNA (anti-oncomir) in malignantly transformed cells. The identification of tumor suppressive miRNAs could provide new insight into the molecular mechanisms of chemical carcinogenesis.


Assuntos
7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/toxicidade , Brônquios/efeitos dos fármacos , Carcinógenos/toxicidade , Transformação Celular Neoplásica/induzido quimicamente , Genes Supressores de Tumor , MicroRNAs/fisiologia , Mucosa Respiratória/efeitos dos fármacos , Animais , Brônquios/metabolismo , Adesão Celular , Linhagem Celular , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/prevenção & controle , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Mucosa Respiratória/metabolismo , Fase de Repouso do Ciclo Celular , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas ras/antagonistas & inibidores , Proteínas ras/genética , Proteínas ras/metabolismo
19.
Zhonghua Yu Fang Yi Xue Za Zhi ; 45(5): 416-21, 2011 May.
Artigo em Chinês | MEDLINE | ID: mdl-21756784

RESUMO

OBJECTIVE: To explore the effect of miR-542-3p in malignant transformation of human bronchial epithelial cells (16HBE) induced by anti-benzo(a)pyrene-7,8-diol-9,10-epoxide (anti-BPDE). METHODS: The relative expression level of mature miR-542-3p in transformed cells (16HBE-T) and untransformed control cells (16HBE-N) was measured by real-time quantitative polymerase chain reaction (qRT-PCR). miRNA mimic was transiently transfected into 16HBE-T to change the expression level of miR-542-3p, and then the influenced changes of cell proliferation, cell cycle, apoptosis, and soft agar colony formation rate and the migration of transfected cells were analyzed. RESULTS: Before transfection, the expression level of mature miR-542-3p in 16HBE-T was lower (39.08 ± 6.95)% than it in 16HBE-N (t = 15.18, P < 0.05). In comparison with the 16HBE-T group, the expression level of miR-542-3p in miR-542-3p mimic-transfected group was (5.23 ± 0.55) fold (t = 17.37, P < 0.05) after transfection. Cell proliferation of mimic-transfected group was decreased to (62.06 ± 5.61)% (t = -17.28, P < 0.05), percentage of cells in G(0)/G(1) phase up to (74.76 ± 4.86)% (t = 4.53, P < 0.05), rate of colony formation degrade to (5.87 ± 0.67)% (t = -6.66, P < 0.05), coverage areas ratio decreased to (0.31 ± 0.08) (t = -6.78, P < 0.05). There was no change with apoptosis. CONCLUSION: Our studies showed that miR-542-3p played the role as a tumor suppressor, which led to a significant decrease in the proliferation capacity and degree of malignancy. These findings suggest aberrantly down-regulated miR-542-3p may be one critical factor that contributes to malignant transformation of 16HBE induced by anti-BPDE.


Assuntos
7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/efeitos adversos , Transformação Celular Neoplásica/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , MicroRNAs/genética , Brônquios/citologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Células Epiteliais/citologia , Humanos , Transfecção
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