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1.
Hum Mutat ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32196811

RESUMO

The aberrant expression of matrix metalloproteinases (MMPs) is known to contribute to the pathogenesis of airway remodeling and alveolar disruption in chronic obstructive pulmonary disease (COPD). In the discovery stage, 11 COPD from five families were subjected to whole-genome sequencing (WGS), and 21 common polymorphisms in MMPs and TIMPs were identified. These polymorphisms were genotyped in two subsequent verification studies. Of these polymorphisms, c.2392G>A (rs2664370T>C)and c.4158C>A (rs2664369T>G) in MMP16 remained significantly different. Functionally, we found that MMP16 expression was significantly increased in peripheral blood monocytes (PBMCs) from COPD and in cigarette smoke extract (CSE)-treated 16HBE cells compared to controls. This was also shown by bioinformatic analysis. COPD carrying rs2664370CC showed decreased levels of MMP16 in the plasma and in PBMCs compared to those carrying CT and TT. Treatment with hsa-miR-576-5p mimics led to a greater reduction in luciferase reporter activity in cells transfected with rs2664370CC. Moreover, blood levels of base excess, PCO2 , and PO2 in COPD with rs2664370CC were significantly lower than those with rs2664370CT+TT. Taken together, these results demonstrate that the rs2664370T>C polymorphism in MMP16 protects against the risk of COPD, likely by favoring an interaction with hsa-miR-576-5p, leading to reduced MMP16 expression and improved blood gas levels. This article is protected by copyright. All rights reserved.

2.
PLoS One ; 15(3): e0230073, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32163467

RESUMO

BACKGROUND: Several anti-D immunoglobulin strategies exist for preventing Rh hemolytic disease of the fetus and newborn. This study systematically assessed the clinical value of those therapeutic strategies. METHODS: The Web of Science, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for eligible studies that evaluated the value of different anti-D immunoglobulin strategies in preventing maternal anti-D antibody sensitization. Combined odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated. The network meta-analysis was conducted using Stata 14.2 and WinBUGS 1.4.3 software. RESULTS: Twenty-four original studies involving 64860 patients were included. Among all therapeutic measures, injecting 300 µg anti-D immunoglobulin at 28 and 34 gestational weeks (antenatal 5/E) appeared to be the most effective measure for preventing maternal antibody sensitization (surface under the cumulative ranking curve [SUCRA] = 96.8%), while a single injection at 28 gestational weeks (SUCRA = 89.2%) was the second most effective. Administering no injection or a placebo (SUCRA = 0.0%) was the least effective intervention measure. CONCLUSION: Among the therapeutic measures, antenatal 5/E appeared to be the best method for reducing the positive incidence of anti-D antibodies in the maternal serum; thus, it may be the most effective treatment for preventing fetal hemolytic disease.

3.
J Trop Pediatr ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040187

RESUMO

Previous studies have shown that the CareStart™ G6PD Deficiency rapid diagnostic test has high diagnostic accuracy on G6PD deficiency in Africa and Thailand, but not in China. As there are regional differences of G6PD genotype distribution, we are attending to verify the effectiveness of the kit in Chinese population. The study cohort included 247 newborns admitted to our hospital for jaundice. The quantitative detection of G6PD enzyme activity and G6PD gene mutations analysis was used to classify the status of G6PD deficiency. The performance of CareStart™ assays was verified by calculating the sensitivity, specificity and area under the receiver operating characteristic curve (AUC) based on the corrected G6PD deficiency status. In male newborns, the sensitivity of the CareStart™ assay was 98.9%, the specificity was 94.2% and the AUC was 0.97. In female newborns, the sensitivity was 58.5% when the cutoff value of residual enzyme activity was 100%; however, the sensitivity was 100% when the cutoff value was 60%. Therefore, the CareStart™ test can effectively screen G6PD deficiency in male newborns and female infants with less than 60% residual enzyme activity, female infants with residual enzyme activities of 60-100% are more likely to be missed diagnosed among Chinese newborns.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31993662

RESUMO

Social deficits are features of autism and highly heritable traits. A common variant in autism-related CNTNAP2 gene, rs2710102, has been linked with social performance, but the neural substrates are largely unknown. We investigated variations in social performance and functional connectivity (static and dynamic) in the subregions of right temporoparietal junction (RTPJ), a key node of brain social network, using resting-state MRI (n = 399) by genotype at rs2710102 in healthy volunteers. Social performance was evaluated using the social domain of the Autism-Spectrum Quotient (AQ-social) (n = 641) and fixation time on eye areas during an eye-tracking task (n = 32). According to previous evidence that the A-allele is the risk allele for social dysfunction, we classified participants into GG and A-allele carriers (AA/AG) groups. The A-allele carriers showed poor social performance (high AQ-social and short fixation time on eye areas) compared with the GG carriers. In the A-allele carriers, decreased stationary functional connectivity between the orbitofrontal cortex and posterior RTPJ (pRTPJ), and decreased dynamic functional connectivity (dFC) between the medial prefrontal cortex (mPFC) and pRTPJ were observed. The fixation time at eye areas positively were correlated with the pRTPJ-mPFC dFC. These findings provided insight for genetic effect on social behavior and its potential neural substrate.

5.
Front Oncol ; 9: 1072, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681605

RESUMO

Early-stage ovarian serous carcinoma is usually difficult to detect in clinical practice. The profiling of protein expression in high-grade serous carcinoma (HGSC) and low-grade serous carcinoma (LGSC) would provide important information for diagnoses and chemotherapy. Here, we performed proteomic profiling of specimens from 13 HGSC and 7 LGSC patients by iTRAQ. A total of 323 proteins that were differentially expressed were identified. After immunohistochemical confirmation of expressed proteins in 166 clinical tissues, asparagine synthetase (ASNS) and filamin A (FLNA) were selected for further functional study. Cisplatin-sensitive (CS; ASNShigh and FLNAlow) and cisplatin-resistant (CR; ASNSlow and FLNAhigh) SKOV3 and OVCAR3 ovarian cancer cell lines were used for subsequent in vitro and in vivo experiments. Notably, ASNS overexpression (ASNS+) or FLNA knockdown (shFLNA) enabled cisplatin-induced apoptosis and autophagy in CR cells. However, ASNS+ and shFLNA promoted and attenuated tumor growth, respectively. In CS cells, ASNS knockdown (shASNS) attenuated clonogenicity, cell proliferation, and the epithelial-mesenchymal transition, whereas FLNA overexpression (FLNA+) protected cells from cisplatin. In vivo, cisplatin resistance was attenuated in mice xenografted with ASNS+, shFLNA, or ASNS+-shFLNA CR cells, whereas xenografts of shASNS or FLNA+ CS cells exhibited resistance to cisplatin. Clinically, all HGSC patients (83/83) responded to cisplatin, while 6 in 41 LGSC patients exhibited cisplatin resistance. These findings identify ASNS and FLNA as distinct biomarkers for HGSC and LGSC, which may have potential value in the prognosis and clinical treatment of serous carcinoma.

6.
Life Sci ; 232: 116650, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302196

RESUMO

BACKGROUND: Inhalation of NO2 leads to a progressive airflow limitation and the development of emphysema-like lesions. We report on the efficacy of hydrogen sulfide (NaHS) for alleviating NO2-induced pulmonary impairment. METHODS: Sprague Dawley rats were exposed to 20 ppm NO2 for 6 h over six consecutive days for 75 days. At day 75, rats who had developed NO2-induced emphysema were then divided into sodium hydrosulfide (NaHS) administrated group, placebo (NaCl) group and spontaneous recovery group for about one month (days 76-105); Pulmonary function (PF) and hematological and biochemical indices were measured at days 14, 45, 75, and 105. RESULTS: NO2 exposure for 75 days was associated with a significant decrease in FEV100/FVC%, an increased in functional residual capacity (FRC), and histologic evidence of emphysema, moreover; NO2 exposure led to elevated triglyceride (TG), red blood cell (RBC), hemoglobin (HGB), and hematocrit (HCT) levels. Impaired rats treated with NaHS showed no further deterioration in PF compared to rats exposed to ambient air and elevated WBC, granulocyte and lymphocyte counts and HDL-C levels to rats given NaCl. CONCLUSIONS: NO2 exposure causes emphysema and a decline in PF in rats. NaHS could alleviate the PF decline as possible indicated by an elevation of HDL-C levels and leukocyte. NaHS has therapeutic potential for emphysema caused by air pollutant NO2.


Assuntos
Testes Hematológicos , Pulmão/efeitos dos fármacos , Dióxido de Nitrogênio/toxicidade , Sulfetos/administração & dosagem , Sulfetos/farmacologia , Administração por Inalação , Animais , Pulmão/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Testes de Função Respiratória
7.
Nanoscale Res Lett ; 14(1): 248, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31342195

RESUMO

Herein, a magnetic graphene field-effect transistor biosensor was prepared through the transfer of a chemical vapor deposition graphene film onto a glass substrate to produce a sensing film and conductive channel. By fixing 1-pyrenebutanoic acid succinimidyl ester onto graphene film as an anchor, a probe aptamer was immobilized on the graphene film in order to capture magnetically labeled complementary single-stranded DNA. Our experiments showed that, within a periodic magnetic field, the biosensor impedance exhibited a periodic oscillation, the amplitude of which was correlated to the complementary DNA concentration. Based on this principle, the magnetic graphene field-effect transistor was utilized to detect single-stranded DNA with detection limition of 1 pM. The results were rationalized using a model wherein the magnetic force causes the DNA strand to bend, thereby resulting in magnetic nanobeads/DNA modulation of the double conductive layer of graphene transistors. Furthermore, since a periodic magnetic field could be introduced to produce a periodic impedance changes of MGFETs, sampling integration could be used to improve the signal-to-noise ratio efficiently by increasing the number of periods of the external magnetic field. Therefore, a novel biosensor for DNA detection with high sensitivity has been presented in this work. Based on the detection principle, this system may also be a potential tool for detecting other bio-molecules, cells, etc.

8.
Medicine (Baltimore) ; 98(19): e15535, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083204

RESUMO

RATIONALE: Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare disease originating from dendritic cells (DCs). There are few cases report interdigitating dendritic cell sarcoma of spleen along with their pathological characteristics and treatment. PATIENT CONCERNS: Here we report a case of IDCS in 53-year-old female who presented spleen enlargement and thrombocytopenia. DIAGNOSES: The patient underwent surgical resection of spleen, and the pathology confirmed IDCS. INTERVENTIONS: She received surgical resection of spleen and one cycle of chemotherapy (ABVD with ifosfamide and oxaliplatin) after surgery. OUTCOMES: She died of severe hepatic failure caused by chemotherapy. DISCUSSION: IDCS is a rare disease with insufficient treatment guidelines. We adopted chemotherapy of ABVD with ifosfamide and oxaliplatin which showed no improvement but led to life-threatening liver damage.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Sarcoma de Células Dendríticas Interdigitantes/terapia , Falência Hepática/induzido quimicamente , Neoplasias Esplênicas/terapia , Bleomicina/efeitos adversos , Dacarbazina/efeitos adversos , Sarcoma de Células Dendríticas Interdigitantes/diagnóstico , Sarcoma de Células Dendríticas Interdigitantes/patologia , Doxorrubicina/efeitos adversos , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Baço/patologia , Esplenectomia , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/patologia , Vimblastina/efeitos adversos
9.
Methods ; 166: 40-47, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30922998

RESUMO

Due to the large numbers of transcription factors (TFs) and cell types, querying binding profiles of all valid TF/cell type pairs is not experimentally feasible. To address this issue, we developed a convolutional-recurrent neural network model, called FactorNet, to computationally impute the missing binding data. FactorNet trains on binding data from reference cell types to make predictions on testing cell types by leveraging a variety of features, including genomic sequences, genome annotations, gene expression, and signal data, such as DNase I cleavage. FactorNet implements several convenient strategies to reduce runtime and memory consumption. By visualizing the neural network models, we can interpret how the model predicts binding. We also investigate the variables that affect cross-cell type accuracy, and offer suggestions to improve upon this field. Our method ranked among the top teams in the ENCODE-DREAM in vivo Transcription Factor Binding Site Prediction Challenge, achieving first place on six of the 13 final round evaluation TF/cell type pairs, the most of any competing team. The FactorNet source code is publicly available, allowing users to reproduce our methodology from the ENCODE-DREAM Challenge.

10.
J Biomater Sci Polym Ed ; 30(8): 608-628, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30907698

RESUMO

Systemic anticoagulation is not suitable for hemodialysis (HD) patients with a high risk of bleeding in the clinic. An HD membrane that provides a localized anticoagulation membrane surface may be a promising strategy to solve this intractable problem for HD patients. Herein, we modified a nonthrombogenic polyethersulfone (PES) dialyzer membrane by grafting argatroban (AG) and methoxy polyethylene glycol amine (mPEG-NH2) via a polydopamine (PDA) strategy. The PES substrates were immersed in an alkaline dopamine solution for 24 h, and then, AG and mPEG-NH2 were sequentially grafted covalently onto the resultant membrane. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) were utilized to confirm the successful introduction of PDA and the immobilization of AG and mPEG-NH2. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to observe the surface structure and morphology after the surface modification. The excellent antithrombotic abilities of the modified membrane were demonstrated by the suppression of platelet adhesion and activation, prolongation of clotting times, and inhibition of thrombin generation and complement activation. This work describes an efficient and convenient method to immobilize AG and mPEG-NH2 to create a nonthrombogenic biointerface for blood-contacting devices such as HD membranes.

11.
Talanta ; 195: 419-425, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30625564

RESUMO

A detection method for 17ß-estradiol (E2) using surface-enhanced Raman scattering (SERS)-based aptamer sensor was presented. Raman reporter molecule Cy3 labeled E2-aptamer and DNA functionalized gold-silver core-shell nanoparticles (Au@Ag CS NPs) offered SERS with high sensitivity and selectivity. Based on the fabricated double strand DNA-immobilized gold-silver core-shell nanoparticles (Au@Ag NPs), SERS signal intensity of Raman reporter changed with the number of Cy3-labeled aptamer attached to the core-shell nanoparticles due to the strong binding affinity between the aptamers and E2 with different concentrations. A wide linear range from 1.0 × 10-13 to 1.0 × 10-9 was obtained for the detection of E2, with a low detection limit of 2.75 fM. This proposed method showed highly sensitive and selective for detecting E2, and could be used to determine E2 in actual samples.


Assuntos
Aptâmeros de Nucleotídeos/química , DNA/química , Estradiol/análise , Ouro/química , Nanopartículas Metálicas/química , Prata/química , Estradiol/química , Análise Espectral Raman
12.
Bioinformatics ; 35(6): 953-961, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30165477

RESUMO

MOTIVATION: With the development of droplet based systems, massive single cell transcriptome data has become available, which enables analysis of cellular and molecular processes at single cell resolution and is instrumental to understanding many biological processes. While state-of-the-art clustering methods have been applied to the data, they face challenges in the following aspects: (i) the clustering quality still needs to be improved; (ii) most models need prior knowledge on number of clusters, which is not always available; (iii) there is a demand for faster computational speed. RESULTS: We propose to tackle these challenges with Parallelized Split Merge Sampling on Dirichlet Process Mixture Model (the Para-DPMM model). Unlike classic DPMM methods that perform sampling on each single data point, the split merge mechanism samples on the cluster level, which significantly improves convergence and optimality of the result. The model is highly parallelized and can utilize the computing power of high performance computing (HPC) clusters, enabling massive inference on huge datasets. Experiment results show the model outperforms current widely used models in both clustering quality and computational speed. AVAILABILITY AND IMPLEMENTATION: Source code is publicly available on https://github.com/tiehangd/Para_DPMM/tree/master/Para_DPMM_package. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Transcriptoma , Análise por Conglomerados , Software
13.
Med Phys ; 46(2): 576-589, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30480818

RESUMO

PURPOSE: Radiation therapy (RT) is a common treatment option for head and neck (HaN) cancer. An important step involved in RT planning is the delineation of organs-at-risks (OARs) based on HaN computed tomography (CT). However, manually delineating OARs is time-consuming as each slice of CT images needs to be individually examined and a typical CT consists of hundreds of slices. Automating OARs segmentation has the benefit of both reducing the time and improving the quality of RT planning. Existing anatomy autosegmentation algorithms use primarily atlas-based methods, which require sophisticated atlas creation and cannot adequately account for anatomy variations among patients. In this work, we propose an end-to-end, atlas-free three-dimensional (3D) convolutional deep learning framework for fast and fully automated whole-volume HaN anatomy segmentation. METHODS: Our deep learning model, called AnatomyNet, segments OARs from head and neck CT images in an end-to-end fashion, receiving whole-volume HaN CT images as input and generating masks of all OARs of interest in one shot. AnatomyNet is built upon the popular 3D U-net architecture, but extends it in three important ways: (a) a new encoding scheme to allow autosegmentation on whole-volume CT images instead of local patches or subsets of slices, (b) incorporating 3D squeeze-and-excitation residual blocks in encoding layers for better feature representation, and (c) a new loss function combining Dice scores and focal loss to facilitate the training of the neural model. These features are designed to address two main challenges in deep learning-based HaN segmentation: (a) segmenting small anatomies (i.e., optic chiasm and optic nerves) occupying only a few slices, and (b) training with inconsistent data annotations with missing ground truth for some anatomical structures. RESULTS: We collected 261 HaN CT images to train AnatomyNet and used MICCAI Head and Neck Auto Segmentation Challenge 2015 as a benchmark dataset to evaluate the performance of AnatomyNet. The objective is to segment nine anatomies: brain stem, chiasm, mandible, optic nerve left, optic nerve right, parotid gland left, parotid gland right, submandibular gland left, and submandibular gland right. Compared to previous state-of-the-art results from the MICCAI 2015 competition, AnatomyNet increases Dice similarity coefficient by 3.3% on average. AnatomyNet takes about 0.12 s to fully segment a head and neck CT image of dimension 178 × 302 × 225, significantly faster than previous methods. In addition, the model is able to process whole-volume CT images and delineate all OARs in one pass, requiring little pre- or postprocessing. CONCLUSION: Deep learning models offer a feasible solution to the problem of delineating OARs from CT images. We demonstrate that our proposed model can improve segmentation accuracy and simplify the autosegmentation pipeline. With this method, it is possible to delineate OARs of a head and neck CT within a fraction of a second.


Assuntos
Aprendizado Profundo , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Processamento de Imagem Assistida por Computador/métodos , Automação , Humanos , Fatores de Tempo , Tomografia Computadorizada por Raios X
14.
J Asthma ; 56(1): 69-78, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29420077

RESUMO

OBJECTIVE: To assess the efficacy and safety profile of tiotropium when added to low- to medium-dose inhaled corticosteroid (ICS) regimen versus low- to medium-dose ICS alone for adults with mild to moderate uncontrolled persistent asthma. DATA SOURCES: The online databases Pubmed, Embase and the Cochrane Library were searched for relevant data published up to November 14, 2017; we also conducted a supplementary search using clinicaltrials.gov. STUDY SELECTIONS: Only randomized control trials were included in this review. RESULTS: Four studies met our inclusion criteria for this review. In our review, two crossover studies were rated as "high risk" in the domain of "other bias" because a washout was not performed between each intervention. Lung function was significantly improved in the patient group receiving low- to medium-dose ICS with tiotropium. Results were consistent between each of three subgroups (tiotropium dry powder inhaler 18 µg or Respimat Soft Mist inhaler 5 µg, Respimat Soft Mist inhaler 2.5 µg, and Respimat Soft Mist inhaler 1.25 µg). Although no significant difference in Asthma Control Questionnaire (ACQ) score was found between the two treatment groups, substantial heterogeneity was observed. The incidence of serious adverse events between the two treatment groups was not statistically significant. CONCLUSIONS: Tiotropium as a once daily add-on to low- to medium-dose ICS may be efficacious and well-tolerated treatment in adults with moderate uncontrolled asthma. However, as only a few studies were identified, more studies of better design and long-term trial duration are required in the future.


Assuntos
Corticosteroides/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Brometo de Tiotrópio/uso terapêutico , Administração por Inalação , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Humanos , Nebulizadores e Vaporizadores , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Testes de Função Respiratória , Brometo de Tiotrópio/administração & dosagem , Brometo de Tiotrópio/efeitos adversos
15.
Curr Med Sci ; 38(3): 443-448, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30074210

RESUMO

This study was designed to analyze the effect of the mitochondrial respiratory pathways of Candida albicans (C. albicans) on the biofilm formation. The 2, 3-bis (2-methoxy- 4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay was used to measure the metabolic activities of biofilms formed by the C. albicans which were cultured in the presence of respiratory pathways inhibitors. The biofilms formed by the wide type (WT), GOA7-deleted (GOA31), GOAV-reconstituted (GOA32), AOXla-deleted (AOX1) and AOXlb-deleted (AOX2) C. albicans strains were examined by the XTT reduction assay and fluorescence microscopy. The expression of adhesion-related genes BCR1, ALS1, ALS3, ECE1 and HWP1 in the biofilms formed by the above five C. albicans strains was detected by real time polymerase chain reaction. It was found that the metabolic activity of biofilms formed by C. albicans was decreased in the presence of alternative oxidase inhibitor whereas it was increased in the presence of classical mitochondrial respiratory pathway complex HI or complex IV inhibitor. AOX1 strain produced scarce biofilms interspersed with few hyphal filaments. Moreover, no significant changes in the expression of BCR1 and ALS3 were observed in the AOX1 strain, but the expression of ALSI and ECE1 was down-regulated, and that of HWP1 was up-regulated. These results indicate that both AOX1 and AOX2 can promote the biofilm formation. However, AOXla primarily plays a regulatory role in biofilm formation in the absence of inducers where the promoting effect is mainly achieved by promoting mycelial formation.


Assuntos
Biofilmes/crescimento & desenvolvimento , Candida albicans/enzimologia , Candida albicans/fisiologia , Proteínas Mitocondriais/metabolismo , Oxirredutases/metabolismo , Proteínas de Plantas/metabolismo , Candida albicans/genética , Transporte de Elétrons , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Genes Fúngicos
16.
Crit Rev Food Sci Nutr ; 58(16): 2800-2813, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28665689

RESUMO

The ability to analyze food safety and quality in a quick, sensitive, and reliable manner is of high importance in food industry. Surface-enhanced Raman scattering (SERS), which is popular for its significant enhancement, excellent sensitivity, and the fingerprinting ability to identify special molecules, has shown vast potential for rapid detection of chemical constitutes, chemical contaminants, and pathogens in food sample. For SERS, the enhancement of Raman signals is related to not only the SERS-active substrates, but also the interactions between sample and substrates. In the current review, colloidal and solid surface-based substrates are briefly described, fabrication techniques for SERS substrates are presented, and applications of SERS for food matrixes, correlation between substrates and food samples are also introduced. Finally, some outlook on further developments is presented. The current review is therefore intended to provide a comprehensive overview on the nanofabrication of SERS substrates, and the potential of applying SERS as an important food analysis platform.


Assuntos
Análise de Alimentos/métodos , Contaminação de Alimentos/análise , Inocuidade dos Alimentos , Análise Espectral Raman/métodos , Humanos
17.
Mol Cell ; 69(1): 62-74.e4, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29276085

RESUMO

Alternative mRNA processing is a critical mechanism for proteome expansion and gene regulation in higher eukaryotes. The SR family proteins play important roles in splicing regulation. Intriguingly, mammalian genomes encode many poorly characterized SR-like proteins, including subunits of the mRNA 3'-processing factor CFIm, CFIm68 and CFIm59. Here we demonstrate that CFIm functions as an enhancer-dependent activator of mRNA 3' processing. CFIm regulates global alternative polyadenylation (APA) by specifically binding and activating enhancer-containing poly(A) sites (PASs). Importantly, the CFIm activator functions are mediated by the arginine-serine repeat (RS) domains of CFIm68/59, which bind specifically to an RS-like region in the CPSF subunit Fip1, and this interaction is inhibited by CFIm68/59 hyper-phosphorylation. The remarkable functional similarities between CFIm and SR proteins suggest that interactions between RS-like domains in regulatory and core factors may provide a common activation mechanism for mRNA 3' processing, splicing, and potentially other steps in RNA metabolism.


Assuntos
Processamento Alternativo/genética , Regulação da Expressão Gênica/genética , Poliadenilação , RNA Mensageiro/metabolismo , Fatores de Poliadenilação e Clivagem de mRNA/metabolismo , Animais , Linhagem Celular , Elementos Facilitadores Genéticos/genética , Técnicas de Inativação de Genes , Células HEK293 , Humanos , Fosforilação , Poli A/metabolismo , Domínios Proteicos/genética , Proteínas de Ligação a RNA/metabolismo , Células Sf9 , Spodoptera
18.
Oncol Rep ; 38(6): 3297-3308, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29039544

RESUMO

Formyl peptide receptor 2 (FPR2) has been identified as a member of the G protein-coupled chemoattractant receptor (GPCR) family and has been implicated as playing a role in both inflammation and cancer development. Epithelial ovarian cancer (EOC) has been suggested to be correlated with both infectious and non-infectious inflammation. To date, the role of FPR2 in EOC remains poorly understood and controversial. In the present study, we aimed to investigate the potential of FPR2 in regulating EOC. We performed immunohistochemistry and RT-qPCR to analyzed expression of FPR2 in EOC tissues and the correlation between FPR2 and EOC clinicopathological characteristics as well as prognosis were also analyzed. To test the role of FPR2 in EOC cell migration, we established FPR2-knockdown SKOV3 cells and performed wound-healing, Transwell and angiogenesis assays to detect the metastatic potential of these EOC cells. Our studies found that FPR2 was overexpressed in EOC tissues and was positively correlated with EOC clinicopathological characteristics including the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade and ovarian cancer type. Survival analyses suggested that FPR2 overexpression indicated the poorer prognosis of EOC patients and FPR2 may act as an independent risk factor for EOC prognosis. FPR2 knockdown decreased the migration potential of the ovarian cancer cells. Moreover, serum amyloid A (SAA) may stimulate the migration of SKOV3 cells through FPR2. The present study suggested that FPR2 promoted the invasion and metastasis of EOC and it could be a prognostic marker for EOC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Prognóstico , Receptores de Formil Peptídeo/genética , Receptores de Lipoxinas/genética , Adulto , Idoso , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Metástase Neoplásica , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Proteína Amiloide A Sérica/administração & dosagem
19.
Clin Epigenetics ; 9: 89, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28855971

RESUMO

BACKGROUND: Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder frequently associated with heterozygous loss-of-function mutations of Nipped-B-like (NIPBL), the human homolog of Drosophila Nipped-B. NIPBL loads cohesin onto chromatin. Cohesin mediates sister chromatid cohesion important for mitosis but is also increasingly recognized as a regulator of gene expression. In CdLS patient cells and animal models, expression changes of multiple genes with little or no sister chromatid cohesion defect suggests that disruption of gene regulation underlies this disorder. However, the effect of NIPBL haploinsufficiency on cohesin binding, and how this relates to the clinical presentation of CdLS, has not been fully investigated. Nipbl haploinsufficiency causes CdLS-like phenotype in mice. We examined genome-wide cohesin binding and its relationship to gene expression using mouse embryonic fibroblasts (MEFs) from Nipbl+/- mice that recapitulate the CdLS phenotype. RESULTS: We found a global decrease in cohesin binding, including at CCCTC-binding factor (CTCF) binding sites and repeat regions. Cohesin-bound genes were found to be enriched for histone H3 lysine 4 trimethylation (H3K4me3) at their promoters; were disproportionately downregulated in Nipbl mutant MEFs; and displayed evidence of reduced promoter-enhancer interaction. The results suggest that gene activation is the primary cohesin function sensitive to Nipbl reduction. Over 50% of significantly dysregulated transcripts in mutant MEFs come from cohesin target genes, including genes involved in adipogenesis that have been implicated in contributing to the CdLS phenotype. CONCLUSIONS: Decreased cohesin binding at the gene regions is directly linked to disease-specific expression changes. Taken together, our Nipbl haploinsufficiency model allows us to analyze the dosage effect of cohesin loading on CdLS development.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Síndrome de Lange/genética , Perfilação da Expressão Gênica/métodos , Haploinsuficiência , Proteínas/genética , Animais , Sítios de Ligação , Fator de Ligação a CCCTC/química , Fator de Ligação a CCCTC/genética , Fator de Ligação a CCCTC/metabolismo , Metilação de DNA , Síndrome de Lange/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Camundongos , Regiões Promotoras Genéticas , Ligação Proteica , Ativação Transcricional
20.
Oncol Lett ; 14(2): 1911-1919, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28789426

RESUMO

Ovarian cancer is the most common, and life-threatening, type of female gynecological cancer. The etiology of ovarian cancer remains unclear, and there are currently no effective screening or treatment methods for the disease. Microbial infection serves a marked function in inducing carcinogenesis. A number of studies have identified pelvic inflammatory disease as a risk factor for epithelial ovarian cancer. Thus, it is hypothesized that microbial infection may contribute to ovarian cancer. In the present review, the microorganisms that have been identified to be associated with ovarian cancer and the underlying molecular mechanisms involved are discussed. Infection-induced chronic inflammation is considered an important process for carcinogenesis, cancer progression and metastasis. Therefore, the pathological process and associated inflammatory factors are reviewed in the present paper.

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