Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cancer Manag Res ; 14: 135-155, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35027848

RESUMO

Background: The use of machine learning (ML) in predicting disease prognosis has increased, and scientists have adopted different methods for cancer classification to optimize the early screening of cancer to determine its prognosis in advance. In this study, we aimed at improving the prediction accuracy of gastric cancer in postoperation patients by constructing a highly effective prognostic model. Methods: The study used postoperative gastric cancer patient data from the SEER database. The LASSO regression method was used to construct a clinical prognostic model, and four machine learning methods (Boruta algorithm, neural network, support vector machine, and random forest) were used to screen and recombine the features to construct an ML prognostic model. Clinical information on 955 postoperative gastric cancer patients collected from the Affiliated Tumor Hospital of Harbin Medical University was used for external verification. Results: Experimental results showed that the AUC values of 1, 3 and 5 years in the training set, validation set and external validation set of clinical prognosis model and ML prognosis model directly established by LASSO regression are all around 0.8. Conclusion: Both models can accurately evaluate the prognosis of postoperative patients with gastric cancer, which may be helpful for accurate and personalized treatment of postoperative patients with gastric cancer.

2.
Anal Methods ; 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34877580

RESUMO

The detection of biomolecular analytes is of great importance in clinical, environmental, and argo-food areas, among which the electrochemical methodology is attracting much attention. In particular, screen-printed electrode (SPE)-based sensing applications have exhibited potential possibility for on-site detection, especially for fast clinical biomarker detection, since they provide a miniaturized but robust and portable electrode detection system. In this context, we focused on the modification of SPE with functional antibodies to improve the electrochemical detection performance in versatile sensing applications, particularly for COVID-19 detection. These antibodies were immobilized onto the electrode surface via various methodologies, through which the powerful potential from the modification of SPE was revealed. Finally, more novel and excellent works on the biomolecular modification of SPE and the prospects of this technology from its state-of-art status to commercialization are previewed and future perspectives in this field are mentioned.

3.
Front Genet ; 12: 758926, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745226

RESUMO

Background: The management of gastric cancer (GC) still lacks tumor markers with high specificity and sensitivity. The goal of current research is to find effective diagnostic and prognostic markers and to clarify their related mechanisms. Methods: In this study, we integrated GC DNA methylation data from publicly available datasets obtained from TCGA and GEO databases, and applied random forest and LASSO analysis methods to screen reliable differential methylation sites (DMSs) for GC diagnosis. We constructed a diagnostic model of GC by logistic analysis and conducted verification and clinical correlation analysis. We screened credible prognostic DMSs through univariate Cox and LASSO analyses and verified a prognostic model of GC by multivariate Cox analysis. Independent prognostic and biological function analyses were performed for the prognostic risk score. We performed TP53 correlation analysis, mutation and prognosis analysis on eleven-DNA methylation driver gene (DMG), and constructed a multifactor regulatory network of key genes. Results: The five-DMS diagnostic model distinguished GC from normal samples, and diagnostic risk value was significantly correlated with grade and tumor location. The prediction accuracy of the eleven-DMS prognostic model was verified in both the training and validation datasets, indicating its certain potential for GC survival prediction. The survival rate of the high-risk group was significantly lower than that of the low-risk group. The prognostic risk score was an independent risk factor for the prognosis of GC, which was significantly correlated with N stage and tumor location, positively correlated with the VIM gene, and negatively correlated with the CDH1 gene. The expression of CHRNB2 decreased significantly in the TP53 mutation group of gastric cancer patients, and there were significant differences in CCDC69, RASSF2, CHRNB2, ARMC9, and RPN1 between the TP53 mutation group and the TP53 non-mutation group of gastric cancer patients. In addition, CEP290, UBXN8, KDM4A, RPN1 had high frequency mutations and the function of eleven-DMG mutation related genes in GC patients is widely enriched in multiple pathways. Conclusion: Combined, the five-DMS diagnostic and eleven-DMS prognostic GC models are important tools for accurate and individualized treatment. The study provides direction for exploring potential markers of GC.

5.
Front Genet ; 12: 699910, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335697

RESUMO

Background: The SET and MYND domain-containing (SMYD) gene family comprises a set of genes encoding lysine methyltransferases. This study aimed to clarify the relationship between the expression levels of SMYD family members and the prognosis and immune infiltration of malignant tumors of the digestive system. Methods: The Oncomine, Ualcan, Kaplan-Meier Plotter, cBioPortal, Metascape, and TIMER databases and tools were used to analyze the correlation of SMYD family mRNA expression, clinical stage, TP53 mutation status, prognostic value, gene mutation, and immune infiltration in patients with esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), and stomach adenocarcinoma (STAD). Results: In ESCA, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/3 with the clinical stage, that of SMYD2/3/4/5 with TP53 mutation status, that of SMYD2/4/5 with overall survival (OS), and that of SMYD1/2/3/4 with relapse-free survival (RFS). In LIHC, the mRNA expression of SMYD1/2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/4/5 with the clinical stage, that of SMYD3/5 with TP53 mutation status, that of SMYD2/3/4/5 with OS, and that of SMYD3/5 with RFS. In STAD, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD1/4 with the clinical stage, that of SMYD1/2/3/5 with TP53 mutation status, that of SMYD1/3/4 with OS, and that of SMYD1/3 with RFS. Furthermore, the function of SMYD family mutation-related genes in ESCA, LIHC, and STAD patients was mainly related to pathways, such as mitochondrial gene expression, mitochondrial matrix, and mitochondrial translation. The expression of SMYD family genes was significantly correlated with the infiltration of six immune cell types and eight types of immune check sites. Conclusion: SMYD family genes are differentially expressed and frequently mutated in malignant tumors of the digestive system (ESCA, LIHC, and gastric cancer). They are potential markers for prognostic prediction and have important significance in immunity and targeted therapy.

6.
Analyst ; 145(13): 4671-4679, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32458862

RESUMO

Genotyping of the epidermal growth factor receptor (EGFR) mutation status is of great importance in the screening of appropriate patients with advanced non-small cell lung carcinoma (NSCLC) to receive superior tyrosine kinase inhibitor (TKIs) therapy. Yet conventional assays are generally costly with a relatively long turnaround time for obtaining results, which can lead to a bottleneck for immediately starting TKI therapy in late-staged patients. In this study, we propose an on-site electrochemical platform for sensitive simultaneous genotyping of the two major EGFR mutations (19del and L858R) through plasma ctDNA based on tetrahedral DNA nanostructure decorated screen-printed electrodes (SPE). Linear-after-the-exponential (LATE)-PCR combined with the amplification refractory mutation system (ARMS) was adopted to produce abundant biotin-labeled single-stranded DNA with high amplification efficiency and specificity. Disposable SPE decorated with self-assembled tetrahedral nanostructured DNA probes that showed ordered orientation and good target accessibility enabled the highly efficient hybridization of the specific amplicons through a sandwich-type and quantitatively translated the interfacial hybridization event into electrochemical signals via enzymatic amplification. Taking advantage of the ARMS-based LATE-PCR and the tetrahedral nanostructure-decorated SPE platform, we achieved the accurate detection of around 30 pg DNA of 19del or L858R, or as low as 0.1% of them in the presence of wild-type DNA. Moreover, the EGFR mutation profiles of 13 NSCLC patients we enlisted were accurately genotyped by our electrochemical platform, the results of which were in good agreement with those of commercial genetic detection methods.


Assuntos
DNA Tumoral Circulante/sangue , DNA/química , Técnicas Eletroquímicas/métodos , Receptores ErbB/genética , Técnicas de Genotipagem/métodos , Nanoestruturas/química , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , DNA Tumoral Circulante/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Conformação de Ácido Nucleico , Reação em Cadeia da Polimerase
7.
Sci Rep ; 10(1): 766, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964975

RESUMO

The proteasome inhibitor bortezomib is the most successfully applied chemotherapeutic drug for treating multiple myeloma. However, its clinical efficacy reduced due to resistance development. The underlying molecular mechanisms of bortezomib resistance are poorly understood. In this study, by combining in silico analysis and sgRNA library based drug resistance screening assay, we identified SENP2 (Sentrin/SUMO-specific proteases-2) as a bortezomib sensitive gene and found its expression highly downregulated in bortezomib resistant multiple myeloma patient's samples. Furthermore, down regulation of SENP2 in multiple myeloma cell line RPMI8226 alleviated bortezomib induced cell proliferation inhibition and apoptosis, whereas, overexpression of SENP2 sensitized these cells to bortezomib treatment. We further demonstrate that knockdown of SENP2 in RPMI8226 cells increased SUMO2 conjugated IκBα that resulted in the activation of NF-κB. Taken together, we report that silencing of SENP2 and consequent activation of NF-κB through the modulation of IκBα sumoylation as a novel mechanism inducing bortezomib resistance in multiple myeloma.


Assuntos
Bortezomib/farmacologia , Cisteína Endopeptidases/genética , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Mieloma Múltiplo/genética , Inibidor de NF-kappaB alfa/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Simulação por Computador , Regulação Neoplásica da Expressão Gênica , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , NF-kappa B/metabolismo , RNA Guia/farmacologia , Transdução de Sinais , Sumoilação
8.
Sci Rep ; 9(1): 13830, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554904

RESUMO

Both aberrantly expressed mRNAs and micro(mi)RNAs play important roles in cancer cell function, which makes integration analysis difficult. In this study, we first applied master regulator analysisalgorithm and confirmed hsa-miR-4756-3p as a candidate miRNA in triple negative breast cancer (TNBC) patients; hsa-miR-4756-3p could regulate TNBC cell line apoptosis, proliferation, migration, and cell cycle as well as suppress TGF-ß1 signalling andtumour growth. In TNBC, forkhead box protein M1 (FOXM1)was found to be an hsa-miR-4756-3p target gene, and FOXM1 knockout completely inhibited hsa-miR-4756-3p-induced cell migration and metastasis, TGF-ß1 signalling, and epithelial mesenchymal signal activation, which indicated that hsa-miR-4756-3p functions via the FOXM1-TGFß1-EMT axis.


Assuntos
Biologia Computacional/métodos , Proteína Forkhead Box M1/genética , MicroRNAs/genética , Neoplasias de Mama Triplo Negativas/patologia , Regiões 3' não Traduzidas , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Animais , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Pessoa de Meia-Idade , Transplante de Neoplasias , Neoplasias de Mama Triplo Negativas/genética
9.
Chem Sci ; 8(7): 4764-4770, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28959399

RESUMO

Tumor-related circulating methylated DNA represents only a small fraction of the total DNA in clinical samples (e.g. plasma), challenging the accurate analysis of specific DNA methylation patterns. Yet conventional assays based on the real-time quantitative methylation-specific PCR (qMSP) are generally limited in detection sensitivity and specificity due to its non-specific amplification interference including primer dimers and off-target amplification. Here we propose a single copy-sensitive electrochemical assay for circulating methylated DNA with ultrahigh specificity on the basis of a sequential discrimination-amplification strategy. Methylated DNA rather than unmethylated DNA in a bisulfite-modified sample is identified and amplified by the asymmetric MSP to generate abundant biotin-labeled single-stranded amplicons with reduced primer-dimer artifacts. Self-assembled tetrahedral DNA probes, which are readily decorated on an electrode surface as nanostructured probes with ordered orientation and well controlled spacing, enable the highly efficient hybridization of the specific single-stranded amplicons due to greatly increased target accessibility and significantly decreased noise. The interfacial hybridization event is quantitatively translated into electrochemical signals utilizing an enzymatic amplification. The proposed assay integrates dual sequence discrimination processes and cascade signal amplification processes, achieving the identification of as few as one methylated DNA molecule in the presence of a 1000-fold excess of unmethylated alleles. Furthermore, the excellent assay performance enables tumor related methylation detection in lung cancer patients with 200 microlitre plasma samples. The results are in good consistency with those of clinical diagnosis, whereas the conventional qMSP failed to detect the corresponding methylation pattern of these clinically confirmed positive patients in such trace amounts of samples.

10.
Anal Chem ; 89(19): 10468-10473, 2017 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-28810735

RESUMO

Circulating methylated DNA has been a new kind of cancer biomarker, yet its small fraction of trace total DNA from clinical samples impairs the accurate analysis. Though fluorescence methods based on quantitative methylation specific PCR (qMSP) have been adopted routinely, yet alternative electrochemistry assay of such DNA from clinical samples remains a great challenge. Herein, we report accurate electrochemistry analysis of circulating methylated DNA from clinical plasma samples based on a paired-end tagging and amplifications strategy. Two DNA primers each labeled with digoxigenin (Dig) and biotin are designed for the recognition and amplification of methylated DNA. Paired-end tagging amplicons and avidin-HRP molecules are successively captured on the electrode modified with Anti-Dig. Then HRP executes catalytic reaction to generate amplified signal. The design of paired-end tagging can readily integrate downstream electrochemical amplified reaction, and two heterogeneous amplifications enable high assay sensitivity. As little as 40 pg of methylated genomic DNA (∼10 genomic equivalents) is well identified, and our strategy can even distinguish as low as 1% methylation level. Tumor-specific methylated DNA is clearly detected in the plasma of 10 of 11 NSCLC patients. The high clinical sensitivity of 91% (10/11) indicates the good consistency with clinical diagnosis. Excellent spatial control of electrochemistry allows simpler detection of more methylation patterns compared to fluorescence methods. The developed electrochemical assay is a promising liquid biopsy tool for the analysis of tumor-specific circulating DNA.


Assuntos
Técnicas Biossensoriais/métodos , Metilação de DNA , DNA de Neoplasias/sangue , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Avidina/química , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Primers do DNA/química , Primers do DNA/metabolismo , Digoxigenina/química , Digoxigenina/imunologia , Técnicas Eletroquímicas , Eletrodos , Peroxidase do Rábano Silvestre/química , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Técnicas de Amplificação de Ácido Nucleico
11.
Am J Infect Control ; 43(11): e73-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26521935

RESUMO

BACKGROUND: We investigated the influence of multiple factors on the incidence of occupational blood and body fluid exposures (BBFEs) in health care workers (HCWs) in Guizhou, China, using structural equation modeling (SEM). METHODS: SEM tested in general hospitals was evaluated using survey data from a sample of 1,774 HCWs from 25 hospitals in Guizhou, China, between January and April 2014. RESULTS: The incidence of occupational BBFEs in HCWs was affected by HCWs' knowledge of safe work practices, HCWs' belief in their ability to use safe work practices, HCWs' use of safe work practices, the workplace safety environment, sufficiency of the controls implemented at health care facilities, and workloads. Knowledge of safe work practices had the most influence on the incidence of occupational BBFE in doctors and laboratory technicians. Ability to use safe work practices had the most influence on the incidence of occupational BBFEs in nurses. CONCLUSION: The workplace safety environment, sufficiency of controls implemented at health care facilities, HCWs' knowledge of safe work practices, HCWs' belief in their ability to use safe work practices, HCWs' use of safe work practices, and workload influence the incidence of occupational BBFEs in HCWs.


Assuntos
Líquidos Corporais , Pessoal de Saúde , Exposição Ocupacional , Adulto , China , Feminino , Hospitais , Humanos , Incidência , Masculino , Saúde do Trabalhador , Fatores de Risco
12.
Int J Clin Exp Med ; 8(12): 22450-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26885227

RESUMO

AIMS: To investigate how specific factors, including knowledge, attitude, use of protective devices, safety climate, workload, and nurses' behaviors can influence standard precautions in China through structural equation modeling techniques. BACKGROUND: Although a number of empirical studies have been conducted, an investigation of how multiple variables influence behaviors of standard precautions among the nurses is still needed. METHODS: The study was conducted by selecting registered nurses from 25 public hospitals that operate approximately 500 beds located in different areas of Guizhou Province in China. An anonymous, self-administered questionnaire was distributed to 1000 nurses, and 964 (96.4%) completed questionnaires were returned. exploratory factor analysis was employed to examine associations of attitudes, protective devices, safety climate, workload, and nurses' behaviors with standard precautions. The identified factors were integrated in the proposed structural equation model. FINDINGS: Protective devices had a positive and major influence on nurses' use of standard precautions. Knowledge had a positive impact on the use of standard precautions through attitude mediation, and the safety climate had a positive impact on the use of standard precautions. In contrast, increasing workload had a negative effect on the use of standard precautions. The factors affecting the use of standard precautions among nurses in order of decreasing effect size were: protective devices, knowledge, attitude, safety climate, and workload. CONCLUSIONS: This study offer valuable information for healthcare management regarding the use of standard precautions to reduce occupational exposure among nurses.

13.
BMC Microbiol ; 14: 157, 2014 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-24928416

RESUMO

BACKGROUND: Acquisition of exogenous genetic material is a key event in bacterial speciation. It seems reasonable to assume that recombination of the incoming DNA into genome would be more efficient with higher levels of relatedness between the DNA donor and recipient. If so, bacterial speciation would be a smooth process, leading to a continuous spectrum of genomic divergence of bacteria, which, however, is not the case as shown by recent findings. The goal of this study was todetermine if DNA transfer efficiency is correlated with the levels of sequence identity. RESULTS: To compare the relative efficiency of exogenous DNA acquisition among closely related bacteria, we carried out phage-mediated transduction and plasmid-mediated transformation in representative Salmonella strains with different levels of relatedness. We found that the efficiency was remarkably variable even among genetically almost identical bacteria. Although there was a general tendency that more closely related DNA donor-recipient pairs had higher transduction efficiency, transformation efficiency exhibited over a thousand times difference among the closely related Salmonella strains. CONCLUSION: DNA acquisition efficiency is greatly variable among bacteria that have as high as over 99% identical genetic background, suggesting that bacterial speciation involves highly complex processes affected not only by whether beneficial exogenous DNA may exist in the environment but also the "readiness" of the bacteria to accept it.


Assuntos
DNA/genética , Recombinação Genética , Salmonella/genética , Transdução Genética , DNA/metabolismo , DNA Bacteriano/química , DNA Bacteriano/genética , Especiação Genética , Dados de Sequência Molecular , Salmonella/metabolismo , Análise de Sequência de DNA , Transformação Bacteriana
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...