Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 129
Filtrar
1.
IEEE Trans Image Process ; 30: 1318-1331, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33315565

RESUMO

Few-shot learning for fine-grained image classification has gained recent attention in computer vision. Among the approaches for few-shot learning, due to the simplicity and effectiveness, metric-based methods are favorably state-of-the-art on many tasks. Most of the metric-based methods assume a single similarity measure and thus obtain a single feature space. However, if samples can simultaneously be well classified via two distinct similarity measures, the samples within a class can distribute more compactly in a smaller feature space, producing more discriminative feature maps. Motivated by this, we propose a so-called Bi-Similarity Network (BSNet) that consists of a single embedding module and a bi-similarity module of two similarity measures. After the support images and the query images pass through the convolution-based embedding module, the bi-similarity module learns feature maps according to two similarity measures of diverse characteristics. In this way, the model is enabled to learn more discriminative and less similarity-biased features from few shots of fine-grained images, such that the model generalization ability can be significantly improved. Through extensive experiments by slightly modifying established metric/similarity based networks, we show that the proposed approach produces a substantial improvement on several fine-grained image benchmark datasets. Codes are available at: https://github.com/PRIS-CV/BSNet.

2.
J Colloid Interface Sci ; 585: 85-94, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33279708

RESUMO

Capacitive deionization (CDI) is considered one of the most promising desalination technologies for obtaining fresh water from saline water. In this work, we synthesized a hollow core-shell Co-MOF@Fe/Co-LDH (Co-Fe-LDH) material by developing a strategy to simultaneously grow Co/Fe-LDH on the surface of a Co-MOF precursor in situ. Owing to the increase in the specific surface area of the hollow structure and the Faradaic process of a layered double hydroxide (LDH), the Co-Fe-LDH material exhibits high electrical double layer (EDL) capacitance and pseudocapacitance, which significantly improves the salt adsorption of the material during CDI (34.2 mg/g in a 600 mg/L NaCl solution at 1.2 V). The adsorption for NaCl in this work is approximately 2.5 times the maximum salt adsorption capacity (SAC) of LDH materials applied in nonmembrane CDI (NMCDI). This work may provide a promising model for the application of hollow LDH materials that exhibit pseudocapacitance in CDI.

3.
Scand J Pain ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33141112

RESUMO

Objectives The purpose of this case report is to describe an occurrence of a rare complication of lead extrusion, which was observed 10 months after spinal cord stimulator (SCS) implantation. Methods A patient with low back pain and failed back surgery syndrome underwent implantation of a SCS without complications. Ten months after implantation, one SCS lead extruded from her lower back leading to surgical removal of the leads. Results After identifying the complication of a SCS lead extruding from the patient's back, a surgical revision was performed to remove the SCS leads but retain the implantable pulse generator (IPG) in the gluteal region. During the surgery, it was noted that the anchors were in the appropriate position, sutured and fibrosed to a deep fascial layer. There were no complications from the surgical revision and no infectious process was observed. Conclusions We report the occurrence and management of a rare complication of SCS lead extrusion after SCS implantation for failed back surgery syndrome. After recognition, removal of the leads with retention of the IPG was able to effectively resolve the complication. The revising procedure was well tolerated but resulted in the recurrence of the patient's previous low back pain. We believe that knowledge of this case and its management will aid future physicians in the recognition and management of this rare complication of SCS implantation. Furthermore, as there is a paucity of literature discussing the management of lead extrusion after SCS implantation, we hope that this case report will spur additional research on the management of this complication.

4.
Cancer Manag Res ; 12: 9845-9855, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116843

RESUMO

Purpose: To explore the expression and related mechanism of miR-144-3p and PTEN in thyroid cancer (TC). Patients and Methods: From February 2018 to November 2019, 62 patients with TC who received treatment in Chengwu Hospital Affiliated to Shandong First Medical University were collected. TC cells and human normal thyroid HTori-3 cells were purchased. The miR-144-3p-inhibitor, miR-144-3p-mimics, empty vector plasmid (miRNA-NC), si-PTEN and sh-PTEN were transfected into B-CPAP and HTh-7 cells. The expressions of miR-144-3p and PTEN in the specimens were tested by qRT-PCR (qP). WB was used to detect the expression of Bcl-2, APR3, N-cadherin, Slug and Bax proteins in the cells. The cell proliferation was detected by MTT, and the cell invasion was tested by Transwell. The apoptosis was detected by flow cytometry (FC). Results: miR-144-3p was highly expressed and PTEN was weakly expressed in the patients' tissues. The AUC of miR-144-3p and PTEN was >0.8. miR-144-3p and PTEN were related to TNM stage, lymph node metastasis and differentiation degree of TC patients. The B-CPAP and HTh-7 with the greatest expression differences were selected for transfection. The expression of miR-144-3p in miR-144-3p-inhibitor group was significantly lower than that in NC group (P<0.01), and that in miR-144-3p-mimics group was significantly higher than that in NC group (p < 0.01). The expression of PTEN in si-PTEN group was significantly lower than that in NC group (P<0.01), while that in sh-PTEN group was significantly higher than that in NC group (P<0.01). Silencing miR-144-3p and overexpressing PTEN could inhibit cell proliferation, invasion and promote apoptosis. WB detection uncovered that silencing the miR-144-3p expression and overexpressing PTEN could inhibit the PI3K, Akt, p-AKT, Bcl-2, APR3 and cyclinD1 proteins and promote the up-regulation of Bax expression. Rescue experiments revealed that the cell proliferation, invasion and apoptosis were not different from NC after co-transfection of miR-144-3p-mimics+sh-PTEN and miR-144-3p-inhibitor+si-PTEN into B-CPAP and HTh-7. Conclusion: Inhibition of miR-144-3p expression can up-regulate PTEN and affect cell proliferation, invasion and apoptosis, which may be a potential therapeutic target for TC.

5.
BMJ Open ; 10(9): e036423, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912980

RESUMO

OBJECTIVES: The microscopic evaluation of slides has been gradually moving towards all digital in recent years, leading to the possibility for computer-aided diagnosis. It is worthwhile to know the similarities between deep learning models and pathologists before we put them into practical scenarios. The simple criteria of colorectal adenoma diagnosis make it to be a perfect testbed for this study. DESIGN: The deep learning model was trained by 177 accurately labelled training slides (156 with adenoma). The detailed labelling was performed on a self-developed annotation system based on iPad. We built the model based on DeepLab v2 with ResNet-34. The model performance was tested on 194 test slides and compared with five pathologists. Furthermore, the generalisation ability of the learning model was tested by extra 168 slides (111 with adenoma) collected from two other hospitals. RESULTS: The deep learning model achieved an area under the curve of 0.92 and obtained a slide-level accuracy of over 90% on slides from two other hospitals. The performance was on par with the performance of experienced pathologists, exceeding the average pathologist. By investigating the feature maps and cases misdiagnosed by the model, we found the concordance of thinking process in diagnosis between the deep learning model and pathologists. CONCLUSIONS: The deep learning model for colorectal adenoma diagnosis is quite similar to pathologists. It is on-par with pathologists' performance, makes similar mistakes and learns rational reasoning logics. Meanwhile, it obtains high accuracy on slides collected from different hospitals with significant staining configuration variations.

6.
Nat Commun ; 11(1): 4294, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855423

RESUMO

The early detection and accurate histopathological diagnosis of gastric cancer increase the chances of successful treatment. The worldwide shortage of pathologists offers a unique opportunity for the use of artificial intelligence assistance systems to alleviate the workload and increase diagnostic accuracy. Here, we report a clinically applicable system developed at the Chinese PLA General Hospital, China, using a deep convolutional neural network trained with 2,123 pixel-level annotated H&E-stained whole slide images. The model achieves a sensitivity near 100% and an average specificity of 80.6% on a real-world test dataset with 3,212 whole slide images digitalized by three scanners. We show that the system could aid pathologists in improving diagnostic accuracy and preventing misdiagnoses. Moreover, we demonstrate that our system performs robustly with 1,582 whole slide images from two other medical centres. Our study suggests the feasibility and benefits of using histopathological artificial intelligence assistance systems in routine practice scenarios.


Assuntos
Aprendizado Profundo , Diagnóstico por Computador/métodos , Neoplasias Gástricas/patologia , Bases de Dados Factuais , Reações Falso-Positivas , Humanos , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação
7.
Clin Transl Med ; : e129, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32722861

RESUMO

Esophageal squamous cell carcinoma (ESCC) is more prevalent than esophageal adenocarcinoma in Asia, especially in China, where more than half of ESCC cases occur worldwide. Many studies have reported that the automatic detection of lymph node metastasis using semantic segmentation shows good performance in breast cancer and other adenocarcinomas. However, the detection of squamous cell carcinoma metastasis in hematoxylin-eosin (H&E)-stained slides has never been reported. We collected a training set of 110 esophageal lymph node slides with metastasis and 132 lymph node slides without metastasis. An iPad-based annotation system was used to draw the contours of the cancer metastasis region. A DeepLab v3 model was trained to achieve the best fit with the training data. The learned model could estimate the probability of metastasis. To evaluate the effectiveness of the detection model of learned metastasis, we used another large cohort of clinical H&E-stained esophageal lymph node slides containing 795 esophageal lymph nodes from 154 esophageal cancer patients. The basic authenticity label for each slide was confirmed by experienced pathologists. After filtering isolated noise in the prediction, we obtained an accuracy of 94%. Furthermore, we applied the learned model to throat and lung lymph node squamous cell carcinoma metastases and achieved the following promising results: an accuracy of 96.7% in throat cancer and an accuracy of 90% in lung cancer. In this work, we organized an annotated dataset of H&E-stained esophageal lymph node and trained a deep neural network to detect lymph node metastasis in H&E-stained slides of squamous cell carcinoma automatically. Moreover, it is possible to use this model to detect lymph nodes metastasis in squamous cell carcinoma from other organs. This study directly demonstrates the potential for determining the localization of squamous cell carcinoma metastases in lymph node and assisting in pathological diagnosis.

8.
Front Microbiol ; 11: 439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32346375

RESUMO

Temporal development of the human gut microbiome from infancy to childhood is driven by a variety of factors. We surveyed the fecal microbiome of 729 Chinese children aged 0-36 months, aiming to identify the age-specific patterns of microbiota succession, and evaluate the impact of birth mode, gender, geographical location, and gastrointestinal tract symptoms on the shaping of the gut microbiome. We demonstrated that phylogenetic diversity of the gut microbiome increased gradually over time, which was accompanied by an increase in Bacteroidetes and a reduction in Proteobacteria species. Analysis of community-wide phenotypes revealed a succession from aerobic bacteria and anaerobic bacteria to facultative anaerobes, and from Gram-negative to Gram-positive species during gut microbiota development in early childhood. The metabolic functions of the gut microbiome shifted tremendously alongside early physiological development, including an increase in alanine, aspartate, and glutamate metabolism, and a reduction in glutathione, fatty acid, and tyrosine metabolism. During the first year of life, the Bacteroidetes phylum was less abundant in children born by casarean section compared with those delivered vaginally. The Enterococcaceae family, a group of facultative anaerobic microorganisms with pathogenic potential, was predominant in preterm infants. No measurable effect of maternal antibiotic exposure on gut microbiota development was found in the first 3 years of life. The relative abundances of Coriobacteriaceae and Streptococcaceae families, and Megasphaera genus were found to be higher in girls than in boys. Among the three first-tier Chinese cities, children born and fed in Beijing had a higher abundance of Enterococcaceae and Lachnospiraceae families, and Shenzhen children had a higher abundance of Fusobacteriaceae. The families Alcaligenaceae, Bacteroidaceae, and Porphyromonadaceae were more abundant in children with constipation, whereas the relative abundance of the Clostridium genus was higher in those with diarrhea.

9.
Clin Pharmacokinet ; 59(8): 995-1004, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32328977

RESUMO

The interchangeability evaluation for generic drugs formulated as intravenous injections normally only requires assessments of pharmaceutical equivalence (PE) when the medicinal products are simple small-molecule drugs. However, intravenously administered non-biological complex drugs (NBCDs), such as liposomes, microsphere suspension, or fat emulsion, have inherent passive disposition selectivity due to their special formulations, thereby the in vivo drug performances are improved. Because of the complexity in formulation, the in vitro pharmaceutical investigations of follow-on NBCDs are more complicated than those required for generic small-molecule drugs. In addition to qualitative and quantitative sameness of the active and inactive ingredients, it is required to comparatively study the static and kinetic microscopic particle-related physiochemical properties of the follow-on NBCDs versus the reference products. Moreover, for complex formulations that have a significant impact on the biodistribution of the drug compound, an in vivo bioequivalence (BE) study is also important. Since NBCDs that demonstrated bioequivalence through the conventional BE approach have been found inequivalent in efficacy or safety to the reference products, pivotal BE studies for follow-on NBCDs are required to take both encapsulated/total drug and free drug as the analytes to address release kinetics and biodistribution of the active pharmacological ingredient in the body. This manuscript reviews the 26 U.S. FDA published product-specific guidelines for intravenous injections. In general, these NBCDs can be stratified into four groups according to their release kinetics and ability of bio-membrane penetration. Group 1 consists of seven small-molecule, non-complex drugs; group 2 included four NBCDs with either microscale particle size or rapid dissolution property; group 3 include five loosely packed NBCDs (fat emulsions) and one quickly released ophthalmic liposomal drug; and the last group contains four cytotoxic liposomal or protein-bound NBCDs and five iron carbohydrate complexes. The requirements of the corresponding guidelines range from simple proof of PE between the test and the reference products, to a collection of studies that demonstrate the key manufacturing process (e.g. liposome loading), the particle- or vehicle-wise static and kinetic physiological characterizations, the dissolution test, and BE evaluation of both total/encapsulated drug form and free drug form between the follow-on NBCDs and their reference products. Such studies are challenging in implementation. Therefore, a variety of alternative approaches are proposed in this article.

10.
Arch Physiol Biochem ; : 1-6, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125187

RESUMO

This study aimed to investigate the involvement of long non-coding RNA (lncRNA) lung adenocarcinoma transcript 1 (LUADT1) LUADT1 in diabetic retinopathy (DR). We found LUADT1 may interact with miR-383 by RNA interaction prediction. QPCR analysis showed that lncRNA LUADT1 was downregulated, and miR-383 was upregulated in DR. However, correlation analysis revealed no significant correlation between them. In retinal pigment epithelial cells (RPEpiC, h1RPE7 from Sigma-Aldrich), overexpression of LUADT1 and miR-383 failed to affect the expression of each other. However, LUADT1 overexpression led to increased and miR-383 overexpression led to decreased expression level of peroxiredoxin 3 (PRX3). Cell apoptosis analysis showed that LUADT1 and PRX3 overexpression resulted in the decreased cell apoptosis. MiR-383 played an opposite role and reduced the effects of LUADT1 and PRX3 overexpression. Therefore, LUADT1 regulates PRX3 by serving as the endogenous sponge of miR-383 in DR to regulate cell apoptosis.

11.
Clin Ther ; 42(3): 428-438, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32037096

RESUMO

PURPOSE: Edaravone is a free-radical scavenger with relatively favorable properties of brain penetration. It has been approved for the indications of acute ischemic stroke and amyotrophic lateral sclerosis (ALS). This study aimed to establish a pharmacokinetic (PK) model to fit the PK profile of edaravone after a single sublingual (SL) dose of a novel edaravone tablet and single IV infusion of injectable edaravone in healthy Chinese volunteers participating in a bioavailability study. The model is expected to be useful for predicting the concentration-time profiles of edaravone following different dosing regimens in a healthy Chinese population. The purposes were to identify an optimal dose and dosing regimen for the new SL formulation and to support future clinical exploration of this tablet product in its approved indications and other therapeutic fields being developed. METHODS: The PK profiles after a single SL dose or IV infusion of edaravone 30 mg can be well described by a 3-compartment linear disposition model, on which a first-order absorption model with a lag time and a parameter for bioavailability was incorporated to fit the absorption phase of the SL dose. Performance of these PK models was evaluated for goodness of fit, residual trends, visual predictive checks, as well as precision of model predictions against external data. The validated models were employed for simulating the PK profiles of edaravone after a single SL dose of 60 mg and IV infusion of 60 mg for 60 min. FINDINGS: The resultant estimates support the possibility and feasibility of demonstrating bioequivalence between an SL administration of edaravone 60 mg and the currently approved dosing regimen for ALS (ie, 60 mg IV over 60 min) once per day. The calculation of sample size suggested that the requirement for subject number was acceptable considering the general capacity of a Phase I study center, and so were the procedures defined in the protocol. IMPLICATION: The models can be further applied to simulate favorable concentration-time profiles in diseases with different underlying courses of oxidative stress, and hence facilitate the optimization of current dosing regimens.


Assuntos
Edaravone , Depuradores de Radicais Livres , Administração Sublingual , Adulto , Disponibilidade Biológica , Simulação por Computador , Edaravone/administração & dosagem , Edaravone/sangue , Edaravone/farmacocinética , Depuradores de Radicais Livres/administração & dosagem , Depuradores de Radicais Livres/sangue , Depuradores de Radicais Livres/farmacocinética , Humanos , Injeções Intravenosas , Masculino , Adulto Jovem
12.
J Vet Pharmacol Ther ; 43(2): 208-214, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31943246

RESUMO

Sanguinarine (SA) is a benzo[c] phenanthridine alkaloid which has a variety of pharmacological properties. However, very little was known about the pharmacokinetics of SA and its metabolite dihydrosanguinarine (DHSA) in pigs. The purpose of this work was to study the intestinal metabolism of SA in vitro and in vivo. Reductive metabolite DHSA was detected during incubation of SA with intestinal mucosa microsomes, cytosol, and gut flora. After oral (p.o.) administration of SA, the result showed SA might be reduced to DHSA in pig intestine. After i.m. administration, SA and DHSA rapidly increased to reach their peak concentrations (Cmax , 30.16 ± 5.85, 5.61 ± 0.73 ng/ml, respectively) at 0.25 hr. Both compounds were completely eliminated from the plasma after 24 hr. After single oral administration, SA and DHSA rapidly increased to reach their Cmax (3.41 ± 0.36, 2.41 ± 0.24 ng/ml, respectively) at 2.75 ± 0.27 hr. The half-life (T1/2 ) values were 2.33 ± 0.11 hr and 2.20 ± 0.12 hr for SA and DHSA, respectively. After multiple oral administration, the average steady-state concentrations (Css ) of SA and DHSA were 3.03 ± 0.39 and 1.42 ± 0.20 ng/ml. The accumulation indexes for SA and DHSA were 1.21 and 1.11. The work reported here provides important information on the metabolism sites and pharmacokinetic character of SA. It explains the reasons for low toxicity of SA, which is useful for the evaluation of its performance.

13.
Photochem Photobiol ; 96(1): 113-123, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31441061

RESUMO

UVA can penetrate dermis and cause functional damage of dermal fibroblasts leading photoaging. Ginseng is a widely used traditional Chinese medicine for skin aging. However, its effects on skin photoaging induced by UVA are not clear. In this study, we isolated ginseng proteins (GP), with molecular weights of 27 kDa and 13 kDa, and found that they alleviated the inhibitory effects of UVA on cell viability and increased percentage of NIH-3T3 fibroblasts in the S phase of cells cycle. GP also improved cell contraction ability, increased the expression and secretion of CoL-I, similar to MAPK phosphorylation inhibitors and reduced expression and secretion of MMP-1, MMP-2 and MMP-9 as well as the enzyme activities of MMP-2 and MMP-9. They reduced ROS content, DNA damage and 8-OHdG content, as well as the protein expression of p53, p21 and p16. The levels of p-ERK, p-p38 and p-JNK, p-c-Fos and p-c-Jun proteins were decreased by GP. Inactivated GP did not inhibit the cellular activity and expression and secretion of CoL-I irradiated by UVA. The results showed that GP can improve cell viability and contractile function by inhibiting DNA damage and collagen degradation to inhibit the photoaging effects of skin dermal cells caused by UVA.

14.
Food Chem ; 304: 125383, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31479997

RESUMO

An aqueous two-phase system was used in conjunction with ultrasonic cell disruption to extract and separate solanine (mainly solasonine and solamargine) and Solanum nigrum polysaccharide from Solanum nigrum unripe fruit. The optimized conditions of the present study were determined by a single-factor experiment and a multifactor experiment. The concentration of ethanol was set at 60% and the duration of the ultrasonic cell disruption extraction was 50 min. In the ethanol-K2CO3 aqueous two-phase separation system, the concentration of ethanol was 36%, the concentration of K2CO3 was 0.21 mg·mL-1, and the temperature was 15 °C. The solasonine and solamargine were determined by high-performance liquid chromatography, and the Solanum nigrum polysaccharide was determined by an ultraviolet-visible spectrophotometer in accordance with the phenol-sulfuric acid method. xUnder optimized conditions, the average extraction efficiencies of solasonine, solamargine and Solanum nigrum polysaccharide were 95.86%, 95.95% and 96.95%, respectively, and the average separation efficiencies of solasonine, solamargine and Solanum nigrum polysaccharide were 2.07 mg·g-1, 2.05 mg·g-1 and 8.15 mg·g-1, respectively.


Assuntos
Frutas/química , Polissacarídeos/isolamento & purificação , Solanina/análise , Solanum nigrum/química , Ultrassom , Cromatografia Líquida de Alta Pressão , Polissacarídeos/análise , Alcaloides de Solanáceas/análise , Alcaloides de Solanáceas/isolamento & purificação , Espectrofotometria
15.
ACS Appl Mater Interfaces ; 12(1): 771-779, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31854975

RESUMO

Hole transport layer NiOx-based inverted perovskite solar cells (PSCs) have advantages of simple fabrication, low temperature, and low cost. Furthermore, the p-type NiOx material compared to that of typical n-type SnOx for PSCs has better photostability potential due to its lower photocatalytic ability. However, the NiOx layer modified by some typical materials show relatively simple functions, which limit the synthesized performance of NiOx-based inverted PSCs. Phenethyl ammonium iodide (PEAI) was introduced to modify the NiOx/perovskite interface, which can synchronously contribute to better crystallinity and stability of the perovskite layer, passivating interface defects, formed quasi-two-dimensional PEA2PbI4 perovskite layers, and superior interface contact properties. The PCEs of PSCs with the PEAI-modified NiOx/perovskite interface was obviously increased from 20.31 from 16.54% compared to that of the reference PSCs. The PSCs with PEAI modification remained 75 and 72% of the original PCE values aging for 10 h at 85 °C and 65 days in a relative humidity of 15%, which are superior to the original PCE values (47 and 51%, respectively) for the reference PSCs. Therefore, PSCs with the PEAI-modified NiOx/perovskite interface show higher PCEs and better thermal stability and moisture resistance.

16.
Oncol Lett ; 18(6): 6732-6740, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31807182

RESUMO

The incidence of thyroid disorders, which are common endocrine diseases, has rapidly increased in recent years. However, the etiology and pathogenesis of these disorders remain unclear. Phosphatase and tension homolog (PTEN) is a dual-specific phosphatase that is associated with multiple thyroid disorders; however, the role of PTEN in thyroid disorders remains unknown. In the present study, the human thyroid follicular epithelial cell line Nthy-Ori 3-1 was used to determine the role of PTEN in thyroid disorders. PTEN expression was knocked down using a PTEN-specific short hairpin RNA. Western blotting was subsequently used to determine protein expression, the Matrigel tube formation assay and iodide uptake assay were applied for evaluating the morphology and function of thyroid cells. The results showed that PTEN knockdown decreased the protein expression of paired box 8 (PAX8). The morphology and tubular-like growth pattern of thyroid cells were therefore disrupted, and restoration of PAX8 expression reversed these effects. Furthermore, PTEN-knockdown decreased the expression of specific thyroid proteins (thyroglobulin, TG; thyroid peroxidase, TPO; and sodium/iodide symporter, NIS) and inhibited the iodide uptake ability of thyroid cells by downregulating PAX8, suggesting that PTEN deficiency may impair the function of thyroid cells. In conclusion, the present study reported an important function of PTEN in normal thyroid cells and identified the involvement of PAX8. These results may improve understanding of the role of PTEN in the pathogenesis of thyroid disorders.

17.
Math Biosci Eng ; 16(5): 4607-4621, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31499680

RESUMO

OBJECTIVE: To explore the potential mechanism which miR-527 targeting the heparan sulfate 6-O-endosulfatase (SULF2) regulates TGF-ß/SMAD signaling pathway induced epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC). METHODS: 38 pairs of lung tumor biopsies and corresponding paracancerous biopsies were obtained from NSCLC patients with surgical resection, normal human bronchial epithelial BEAS-2B cells and five NSCLS cell lines were applied for our study. miR-527 and SULF2 expression were determined by qRT-PCR and immunohistochemistry. MiR-527 and SULF2 biological link were predicted by Targetscan.org and tested by dual luciferase. Cells proliferation and apoptosis were respectively detected by EDU staining and flow cytometry. Cells migration was examined by transwell and scratch-wound assay. Expression of proteins related to EMT and TGF-ß/SMAD signaling pathway, such as E-cadherin, N-cadherin, p-Samd3 and p-Smad2, was detected by western blot. RESULTS: miR-527 expression was decreased in lung tumor tissues and NSCLS cell lines, conversely, SULF2 expression was significantly increased. In addition, we found that miR-527 targeted 3'-untranslated regions (3'-UTR) of SULF2 and mediated its expression. Overexpression of miR-527 evidently suppressed NSCLC proliferation, invasion and EMT via TGF-ß/SMAD signaling pathway. Moreover, the silence of SULF2 exhibited a similar effect. CONCLUSION: miR-527 targeting SULF2 down-regulated SULF2 expression, concurrently, suppressed NSCLC epithelial-mesenchymal transition and invasion via inhibiting TGF-ß/SMAD signaling pathway.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Proteína Smad2/metabolismo , Sulfatases/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Regiões 3' não Traduzidas , Biópsia , Brônquios/citologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Neoplásica , Fenótipo , Interferência de RNA , Transdução de Sinais
18.
Math Biosci Eng ; 16(5): 5652-5671, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31499730

RESUMO

Deflection is a crucial indicator to reflect the operating condition of girder bridges, which can be used to evaluate structure condition and identify abnormal loading. The paper analyzed the deflection characteristics of long-span girder bridges based on the coupling vibration between stochastic traffic stream and bridge. First, the latest research advances were integrated to form an analytical model of the coupling vibration between stochastic traffic stream and bridge. Then, a generalized Pareto distribution model based on peaks-over-threshold theory was established to predict the extreme girder deflection. Next, a cellular automaton based microsimulation method was proposed to model the traffic loads on bridges, which utilized the intelligent driver car-following model and acceptance distance based lane-changing model. Finally, these theories were applied in the case study of a long-span prestressed concrete continuous girder bridge. It is discovered from the study that, under the coupling vibration between stochastic traffic stream and bridge, the predicted extreme deflection of the case bridge is far lower than the specified design value. Hence, a grading warning model was established and employed to the analysis of deflection monitoring data of the bridge, showing a wide potential prospect of application.

19.
Mol Med Rep ; 20(5): 4235-4243, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545428

RESUMO

Proper spindle formation and accurate chromosome segregation are essential for ensuring mitotic fidelity. Phosphatase and tensin homolog (PTEN) is a multifunctional protein, which is able to maintain the stability of the genome and chromosomes. The present study described an essential role of PTEN in regulating chromosome segregation to prevent gross genomic instability via regulation of mitotic arrest deficient 2 (MAD2). PTEN knockdown induced cell cycle arrest and abnormal chromosome segregation, which manifested as the formation of anaphase bridges, lagging chromosomes and premature chromatid separation. In addition, MAD2 was identified as a potential target of PTEN. Furthermore, the present study revealed that PTEN knockdown resulted in MAD2 degradation via the ubiquitin­proteasomal pathway, while restoration of MAD2 expression partially ameliorated the mitotic defects induced by PTEN loss. The results from the present study proposed a novel mechanism by which PTEN maintains chromosome stability.


Assuntos
Aberrações Cromossômicas , Segregação de Cromossomos , Regulação da Expressão Gênica , Proteínas Mad2/genética , PTEN Fosfo-Hidrolase/deficiência , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Instabilidade Genômica , Humanos , Fuso Acromático
20.
Toxicol Lett ; 315: 1-8, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31421153

RESUMO

Arsenic trioxide (As2O3) has been used clinically for the treatment of acute promyelocytic leukemia and some solid tumors. However, the mechanisms of its anti-tumor effects are still elusive. Angiogenesis is a key process for tumor initiation, and increasing evidence has supported the role of anti-angiogenesis caused by arsenic in tumor suppression, although the detailed mechanism is not well understood. In the present study, we found that As2O3 significantly inhibited the angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro, and this was mediated by the upregulation of FoxO3a. Knockdown of FoxO3a could restore the angiogenic ability of HUVECs. Moreover, vascular endothelial cell-specific knockout of FoxO3a in mice could disrupt the anti-angiogenesis effect of As2O3 and endow the tumors with resistance to As2O3 treatments. Our results revealed a new mechanism by which As2O3 suppresses angiogenesis and tumor growth.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Trióxido de Arsênio/farmacologia , Trióxido de Arsênio/uso terapêutico , Proteína Forkhead Box O3/efeitos dos fármacos , Leucemia Promielocítica Aguda/tratamento farmacológico , Regulação para Cima/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Veias Umbilicais/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA