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1.
Ecotoxicol Environ Saf ; 213: 111981, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33592372

RESUMO

Environmental pollution due to resistance genes from livestock manure has become a serious issue that needs to be resolved. However, little studies focused on the removal of resistance genes in simultaneous processing of livestock feces and urine. This study investigated the fate of antibiotic resistance genes (ARGs), metal resistance genes (MRGs), and class 1 integron-integrase gene (intI1) during thermophilic fermentation of swine manure in an ectopic fermentation system (EFS), which has been regarded as a novel system for efficiently treating both feces and urine. The abundances of MRGs and tetracycline resistance genes were 34.44-97.71% lower in the EFS. The supplementation of heavy metals significantly increased the abundance of intI1, with the enhancement effect of copper being more prominent than that of zinc. The highest abundances of resistance genes and intI1 were observed at high Cu levels (A2), indicating that Cu can increase the spreading of resistance genes through integrons. Network analysis revealed the co-occurrence of ARGs, MRGs, and intI1, and these genes potentially shared the same host bacteria. Redundancy analysis showed that the bacterial community explained most of the variations in ARGs, and environmental factors had influences on ARGs abundances by modulating the bacterial community composition. The decreased Sphingomonas, Comamonas, Acinetobacter, Lactobacillus, Bartonella, Rhizobium, and Bacteroides were mainly responsible for the reduced resistance genes. These results demonstrate that EFS can reduce resistance genes in simultaneous processing of livestock feces and urine.


Assuntos
Resistência Microbiana a Medicamentos/genética , Fermentação/fisiologia , Genes Bacterianos , Esterco/microbiologia , Metais Pesados/análise , Animais , Antibacterianos/análise , Bactérias/efeitos dos fármacos , Cobre , Integrons , Gado , Esterco/análise , Suínos , Tetraciclina/farmacologia
2.
Eur Radiol ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33449190

RESUMO

OBJECTIVE: To investigate the prognostic significance of T1 mapping using T1 long and short in hypertrophic cardiomyopathy (HCM) patients. METHODS: A total of 263 consecutive patients with HCM referred for cardiovascular magnetic resonance (CMR) imaging were enrolled in this study. The imaging protocol consisted of cine, late gadolinium enhancement (LGE), and T1 mapping with T1 long and short. All patients were followed up prospectively. Outcome events were divided into the primary and secondary endpoint events. Primary endpoint events included cardiac death, heart transplant, aborted sudden death, and cardiopulmonary resuscitation after syncope. The secondary endpoint event was defined as unplanned rehospitalization for heart failure. RESULT: The average follow-up duration was 28.3 ± 12.1 (range: 1-78) months. In all, 17 patients (7.0%) experienced a primary endpoint including 13 cardiovascular deaths, three aborted sudden deaths, and one resuscitation after syncope, and 34 patients experienced a secondary endpoint. Patients with primary endpoints showed a trend towards more extensive LGE (p < 0.001), significantly higher ECV (p < 0.001), and native T1 (p = 0.028) than those without events. In multivariate Cox regression analysis, ECV was independently associated with primary and secondary endpoints (p < 0.001 and p = 0.047, respectively). For every 3% increase, ECV portended a 1.374-fold increase risk of a primary endpoint occurring (p < 0.001). In the Kaplan-Meier survival analysis, the incidence of primary and secondary endpoint events was significantly higher in HCM with increased ECV (p < 0.001 and p = 0.009, respectively). CONCLUSION: In patients with HCM, ECV is a strong imaging marker for predicting adverse outcome. KEY POINTS: • ECV is a potent imaging index which has a strong correlation with LVEF and LVEDVI and can evaluate myocardial tissue structure and function. • ECV and LGE can provide a prognostic value in patients with hypertrophic cardiomyopathy. • ECV has stronger predictive effectiveness than LGE; even in the subgroup with LGE, ECV shows independent predictive significance for adverse events.

3.
Onco Targets Ther ; 13: 12043-12054, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262605

RESUMO

Background: As the fourth most common cancer among women worldwide, cervical cancer lead to 311,000 deaths in 2018. Although the treatments have been developed, the survival rate of cervical cancer remains unsatisfactory. In this study, we aimed to identify differentially expressed lncRNAs (DEIncRNAs) between cervical cancer and adjacent normal tissues using bioinformatics analysis, and further to investigate the biological function of the DEIncRNAs in vitro and in vivo. Methods: The expression profiles from two microarray datasets (GSE6791 and GSE63514) were downloaded from GEO for analysis of DEIncRNAs between cervical cancer and adjacent normal cervical tissues. Among all DEIncRNAs, MIR155HG upregulation was identified and selected for further investigation. The effect of MIR155HG knockdown on proliferation, apoptosis and invasion in SiHa and Hela cells were evaluated. In addition, Western blot, RNA immunoprecipitation (RIP) and cell cycle assays were performed to determine the binding target of MIR155HG. Furthermore, the effect of MIR155HG knockdown on tumor growth in vivo was investigated. Results: The level of MIR155HG was found to be significantly upregulated in cervical cancer tissue compared with adjacent cervical tissue. Knockdown of MIR155HG notably inhibited the proliferation of SiHa and Hela cells by inducing apoptosis. In addition, MIR155HG knockdown decreased cell invasion. Moreover, tumor growth in xenograft was significantly inhibited by MIR155HG knockdown in vivo. Additionally, SRSF1 was identified as the binding protein of MIR155HG. Conclusion: Our findings demonstrated that MIR155HG knockdown inhibited the progression of cervical cancer by binding SRSF1, inspiring the usage of MIR155HG as a potential novel therapy target for the treatment of cervical cancer.

4.
Front Oncol ; 10: 554809, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33102219

RESUMO

The prognosis of hepatocellular carcinoma (HCC) is closely associated with the occurrence of distant metastases, which is likely due to circulating tumor cells (CTCs). However, the low number of CTCs is the main obstacle limiting research of the mechanism of CTC metastasis. Here, We evaluated the role of ubiquitin-specific protease 1 (USP1) in promoting CTC survival during blood-borne metastases. We observed that USP1 was frequently upregulated in CTCs and correlated with metastasis and a reduced overall survival rate of patients. Additionally, genetic knockout of USP1 the survival rate of CTCs. Further analyses showed that USP1 mediates oncogenic activity by deubiquitinating and stabilizing transducin ß-like 1 X-linked receptor 1 (TBLR1), which plays essential roles in regulating Wnt signaling. These results demonstrated that USP1 may act as an essential factor in promoting the survival of CTCs and suggest that inhibition of USP1 is a potential strategy for HCC treatment.

5.
Theranostics ; 10(24): 11264-11277, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042282

RESUMO

Rationale: As the transcriptional products of active enhancers, enhancer RNAs (eRNAs) are essential for the initiation of tumorigenesis. However, the landscape and functional characteristics of eRNAs in Chinese lung adenocarcinoma, and the clinical utility of eRNA-based molecular subtypes remain largely unknown. Methods: A genome-wide profiling of eRNAs was performed in 80 Chinese lung adenocarcinoma patients with RNA-seq data. Functional eRNAs and associated genes were identified between paired adenocarcinoma and adjacent samples. Unsupervised clustering of functional eRNAs was conducted and the associations with molecular characteristics and clinical outcomes were accessed by integrating whole-genome sequencing data and clinical data. Additionally, 481 lung adenocarcinoma patients were used for the validation based on The Cancer Genome Atlas (TCGA) dataset. Results: A total of 3297 eRNAs with sufficient expression were identified, which were globally upregulated in adenocarcinoma samples compared to matched-adjacent pairs (P = 7.61×10-3). Further analyses indicated that these upregulated eRNAs were correlated with copy number amplification (CNA) status (Cor = 0.22, P = 0.045), and eRNA-correlated genes were primarily involved in cell cycle and immune system-related pathways. Based on the co-expression analysis of eRNAs with protein-coding genes, we defined 188 functional eRNAs and their correlated genes were overrepresented in cancer driver genes (ER = 1.98, P = 5.95×10-12) and clinically-actionable genes (ER = 2.19, P = 3.44×10-4). The eRNA-based consensus clustering further identified a novel molecular subtype with immune deficiency and a high-level of genomic alterations, which was associated with poor clinical outcomes of lung adenocarcinoma patients (OS: HR = 1.91, P = 0.015; PFI: HR = 1.64, P = 0.034). Conclusions: The genome-wide identification and characterization of eRNAs reveal novel regulators for the development of lung cancer, which provides a new biological dimension for the understanding of eRNAs during lung carcinogenesis and emphasize the clinical utility of eRNA-based molecular subtypes in the treatment of lung adenocarcinoma.

6.
Radiology ; : 202261, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33078997

RESUMO

Background The prognostic value of myocardial trabecular complexity in patients with hypertrophic cardiomyopathy (HCM) is unknown. Purpose To explore the prognostic value of myocardial trabecular complexity using fractal analysis in participants with HCM. Materials and Methods The authors prospectively enrolled participants with HCM who underwent 3.0-T cardiovascular MRI from August 2011 to October 2017. The authors also enrolled 100 age- and sex-matched healthy participants to form a comparison group. Trabeculae were quantified with fractal analysis of cine slices to estimate the fractal dimension (FD). Participants with HCM were divided into normal and high FD groups according to the upper limit of normal reference value from the healthy group. The primary end point was defined as all-cause mortality and aborted sudden cardiac death. The secondary end point was the composite of the primary end point and readmission to the hospital owing to heart failure. Internal validation was performed using the bootstrapping method. Results A total of 378 participants with HCM (median age, 50 years; age range, 40-61 years; 207 men) and 100 healthy participants (median age, 46 years; age range, 36-59 years; 55 women) were included in this study. During the median follow-up of 33 months ± 18 (standard deviation), the increased maximal apical FD (≥1.325) had a higher risk of the primary and secondary end points than those with a normal FD (<1.325) (P = .01 and P = .04, respectively). Furthermore, Cox analysis revealed that left ventricular maximal apical FD (hazard ratio range, 1.001-1.008; all P < .05) provided significant prognostic value to predict the primary and secondary end points after adjustment for the European Society of Cardiology predictors and late gadolinium enhancement. Internal validation showed that left ventricular maximal apical FD retained a good performance in predicting the primary end points with an area under the curve of 0.70 ± 0.03. Conclusion Left ventricular apical fractal dimension, which reflects myocardial trabecular complexity, was an independent predictor of the primary and secondary end points in patients with hypertrophic cardiomyopathy. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Captur and Moon in this issue.

7.
Front Med ; 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32889700

RESUMO

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32658979

RESUMO

AIMS: To evaluate the prognostic value of left ventricular (LV) remodelling index (RI) in idiopathic dilated cardiomyopathy (DCM) patients. METHODS AND RESULTS: We prospectively enrolled 412 idiopathic DCM patients and 130 age- and sex-matched healthy volunteers who underwent cardiovascular magnetic resonance imaging between September 2013 and March 2018. RI was defined as the cubic root of the LV end-diastolic volume divided by the mean LV wall thickness on basal short-axis slice. The primary endpoint included all-cause mortality and heart transplantation. The secondary endpoint included the primary endpoint and heart failure (HF) readmission. During the median follow-up of 28.1 months (interquartile range: 19.3-43.0 months), 62 (15.0%) and 143 (34.7%) patients reached the primary and secondary endpoints, respectively. Stepwise multivariate Cox regression showed that RI [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.11-1.30, P < 0.001], late gadolinium enhancement (LGE) presence and log (N-terminal pro-B-type natriuretic peptide) were independent predictors of the primary endpoint, while RI (HR 1.15, 95% CI 1.08-1.23, P < 0.001) and extracellular volume were independent predictors of the secondary endpoint. The addition of RI to LV ejection fraction (EF) and LGE presence showed significantly improved global χ2 for predicting primary and secondary endpoints (both P < 0.001). Furthermore, RI derived from echocardiography also showed independent prognostic value for primary and secondary endpoints with clinical risk factors. CONCLUSIONS: RI is an independent predictor of all-cause mortality, heart transplantation, and HF readmission in DCM patients and provides incremental prognostic value to LVEF and LGE presence.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32432393

RESUMO

The rapid development and advances in nanomaterials and nanotechnology in the past two decades have made profound impact in our approaches to individualized disease diagnosis and treatment. Nanomaterials, mostly in the range of 10-200 nm, developed for biomedical applications provide a wide range of platforms for building and engineering functionalized structures, devices, or systems to fulfill the specific diagnostic and therapeutic needs. Driven by achieving the ultimate goal of clinical translation, sub-5 nm nano-constructs, in particular inorganic nanoparticles such as gold, silver, silica, and iron oxide nanoparticles, have been developed in recent years to improve the biocompatibility, delivery and pharmacokinetics of imaging probes and drug delivery systems, as well as in vivo theranostic applications. The emerging studies have provided new findings that demonstrated the unique size-dependent physical properties, physiological behaviors and biological functions of the nanomaterials in the range of the sub-5 nm scale, including renal clearance, novel imaging contrast, and tissue distribution. This advanced review attempts to introduce the new strategies of rational design for engineering nanoparticles with the core sizes under 5 nm in consideration of the clinical and translational requirements. We will provide readers the update on recent discoveries of chemical, physical, and biological properties of some biocompatible sub-5 nm nanomaterials as well as their demonstrated imaging and theranostic applications, followed by sharing our perspectives on the future development of this class of nanomaterials. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanomaterials and Implants.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32316286

RESUMO

Lead smelting slag (LSS) has been identified as general industrial solid waste, which is produced from the pyrometallurgical treatment of the Shuikoushan process for primary lead production in China. The LSS-based geopolymer was synthesized after high-energy ball milling. The effect of unconfined compressive strength (UCS) on the synthesis parameters of the geopolymer was optimized. Under the best parameters of the geopolymer (modulus of water glass was 1-1.5, dosage of water glass (W(SiO2+Na2O)) was 5% and water-to-binder ratio was 0.2), the UCS reached 76.09 MPa after curing for 28 days. The toxicity characteristic leaching procedure (TCLP) leaching concentration of Zn from LSS fell from 167.16 to 93.99 mg/L after alkali-activation, which was below the limit allowed. Meanwhile, C-S-H and the geopolymer of the hydration products were identified from the geopolymer. In addition, the behavior of iron was also discussed. Then, the hydration process characteristics of the LSS-based geopolymer were proposed. The obtained results showed that Ca2+ and Fe2+ occupied the site of the network as modifiers in the glass phase and then dissociated from the glass network after the water glass activation. At the same time, C-S-H, the geopolymer and Fe(OH)2 gel were produced, and then the Fe(OH)2 was easily oxidized to Fe(OH)3 under the air curing conditions. Consequently, the conclusion was drawn that LSS was an implementable raw material for geopolymer production.


Assuntos
Resíduos Industriais/análise , Chumbo , Metalurgia , Dióxido de Silício , Álcalis , China
11.
J Biomed Res ; 34(2): 129-138, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32305967

RESUMO

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that currently lacks effective biomarkers and therapeutic targets required to investigate the diagnosis and treatment of TNBC. Here we performed a comprehensive differential analysis of 165 TNBC samples by integrating RNA-seq data of breast tumor tissues and adjacent normal tissues from both our cohort and The Cancer Genome Atlas (TCGA). Pathway enrichment analysis was conducted to evaluate the biological function of TNBC-specific expressed genes. Further multivariate Cox proportional hazard regression was performed to evaluate the effect of these genes on TNBC prognosis. In this report, we identified a total of 148 TNBC-specific expressed genes that were primarily enriched in mammary gland morphogenesis and hormone levels related pathways, suggesting that mammary gland morphogenesis might play a unique role in TNBC patients differing from other breast cancer types. Further survival analysis revealed that nine genes ( FSIP1, ADCY5, FSD1, HMSD, CMTM5, AFF3, CYP2A7, ATP1A2, and C11orf86) were significantly associated with the prognosis of TNBC patients, while three of them ( ADCY5, CYP2A7, and ATP1A2) were involved in the hormone-related pathways. These findings indicated the vital role of the hormone-related genes in TNBC tumorigenesis and may provide some independent prognostic markers as well as novel therapeutic targets for TNBC.

12.
Sci Rep ; 10(1): 6557, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32300126

RESUMO

Basilar artery (BA) dolichosis is not uncommon in patients with acute isolated pontine infarction. The effect of this abnormal BA geometrical form on the outcomes of pontine infarction has not been closely examined. This study aims to elucidate whether BA dolichosis contributes to a poor 90-day outcome in acute isolated pontine infarction. A total of 101 patients were enrolled with a median age of 65 years. The BA diameter (p = 0.026), basilar artery length (BAL) (p < 0.001), bending length (BL) (p < 0.001) and the proportion of BA bending (p < 0.001) were significantly higher in the BA dolichosis group. A poor outcome was closely associated with the baseline National Institute of Health Stroke Scale (NIHSS) score (p < 0.001), and BL (p = 0.042) as well as the proportions of BA dolichosis (p = 0.007) and BA bending (p = 0.010) in univariate analysis. Multivariate logistic regression analysis determined that BA dolichosis (adjusted OR = 4.724, 95% CI: 1.481~15.071, p = 0.009) and baseline NIHSS score (adjusted OR = 1.805, 95% CI: 1.296~2.513, p < 0.001) were independently associated with a poor outcome at 90 days. In conclusion, BA dolichosis may be a predictor of concern for a poor 90-day outcome in patients with acute isolated pontine infarction.


Assuntos
Artéria Basilar/patologia , Infarto Encefálico/patologia , Ponte/patologia , Doença Aguda , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Fatores de Risco , Resultado do Tratamento
14.
Front Oncol ; 10: 372, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32266149

RESUMO

Background: As the sixth most common cancer of worldwide, head and neck cancers (HNC) are springing from oral cavity, pharynx and larynx and there is no strong biomarker for prognosis. Rates of 5 years survival with HNC remain relatively low in decades with improvement of treatments. Evidence that single nucleotide polymorphisms (SNPs) play a part in cancer prognosis is growing. Methods: We conducted an exome-wide association study among 261 patients with head and neck squamous cell carcinoma (HNSCC) and then validated in The Cancer Genome Atlas (TCGA) database for survival by using the Cox proportional hazards regression models and Kaplan-Meier analyses. Results: After combining the result of the two stages, 4 SNPs were significantly associated with HNSCC survival (rs16879870 at 6q14.3: adjusted HR = 2.02, 95%CI = 1.50-2.73, P = 3.88 × 10-6; rs2641256 at 17p13.2: adjusted HR = 0.67, 95%CI = 0.56-0.80, P = 7.51 × 10-6; rs2761591 at 11p13: adjusted HR = 2.07, 95%CI = 1.50-2.87, P = 1.16 × 10-5; and rs854936 at 22q11.21: adjusted HR = 1.92, 95%CI = 1.43-2.57, P = 1.27 × 10-5). Besides, we constructed a receiver operating characteristic (ROC) model to estimate predictive effect of the novel SNPs combined with clinical stage in HNSCC prognosis (AUC = 0.715). We also found the genotype of rs16879870 and rs854936 was significantly associated with the expression of gene GJB7 (P = 0.013) and RTN4R (P = 0.047) in cancer tissues of TCGA, respectively. Conclusion: Our findings suggested that the SNPs (rs16879870, rs2641256, rs2761591, rs854936) might play a crucial role in prognosis of HNSCC.

15.
Theranostics ; 10(6): 2479-2494, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194814

RESUMO

Rationale: "Active targeting" based on the ligand-target affinity is a common strategy to precisely deliver nanoparticle (NP) imaging probes or drug carriers to the diseased tissue. However, such ligand-mediated active targeting inevitably takes place with prerequisite "passive targeting", driven by the enhanced permeability and retention (EPR) effect. Thus, the efficiency of active targeting in relation to off-targeted unbound NPs is of great importance in quantitative imaging of tumor biomarkers and delivery. With the notion that easy clearance of off-targeted uIONPs may lead to enhanced active targeting and tumor accumulation, we examined the NP size effect on "active targeting" of the transferrin receptor (TfR) using transferrin (Tf)-conjugated sub-5 nm (3 nm core) ultrafine iron oxide NPs (uIONPs) and larger IONPs (30 nm core). Methods: Green fluorescent dye (FITC)-labeled active targeting uIONPs (FITC-Tf-uIONPs) and red fluorescent dye (TRITC)-labeled passive targeting uIONPs (TRITC-uIONPs) were prepared. FITC-Tf-IONPs and TRITC-IONPs were used as comparison for the NP size effect. Multiphoton imaging, confocal fluorescence imaging, histological staining and computational analysis were applied to track different types of NPs in tumors at 1, 3 and 24 hours after co-injection of equal amounts of paired NPs, e.g., active targeting FITC-Tf-uIONPs and non-targeting TRITC-uIONPs, or FITC-Tf-IONPs and TRITC-IONPs into the same mice bearing 4T1 mouse mammary tumors. Results: Active targeting uIONPs exhibited an almost 6-fold higher level of tumor retention with deeper penetration comparing to non-targeting uIONPs at 24 hours after co-injection. However, accumulation of active targeting IONPs with a 30-nm core is only about 1.15-fold higher than non-targeting IONPs. The enhanced active targeting by uIONPs can be attributed to the size dependent clearance of unbound off-targeted NPs, as majority off-targeted uIONPs were readily cleared from the tumor by intravasation back into tumor blood vessels likely due to high interstitial pressure, even though they are not favorable for macrophage uptake. Conclusion: Ligand-mediated active targeting improves the delivery and accumulation of the sub-5 nm NPs. The improvement on active targeting is size-dependent and facilitated by NPs with sub-5 nm core sizes. Thus, sub-5 nm NPs may serve as favorable platforms for development of NP-based molecular imaging probes and targeted drug carriers.

17.
J Cancer ; 11(5): 1075-1081, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31956354

RESUMO

Genome-wide association studies (GWAS) have reported 45 single-nucleotide polymorphisms (SNPs) that may contribute to the susceptibility of lung cancer, with the majority in non-coding regions. However, no study has ever systematically evaluated the association between SNPs in physical chromatin interaction regions and lung cancer risk. In this study, we integrated the chromatin interaction information (Hi-C data) of lung cancer cell line and conducted a meta-analysis with two Asian GWASs (7,127 cases and 6,818 controls) to evaluate the association of potentially functional SNPs in chromatin interaction regions with lung cancer risk. We identified four novel lung cancer susceptibility loci located at 1q21.1 (rs17160062, P=4.00×10-6), 2p23.3 (rs670343, P=4.87×10-7), 2p15 (rs9309336, P=3.24×10-6) and 17q21.2 (rs9252, P=1.51×10-5) that were significantly associated with lung cancer risk after correction for multiple tests. Functional annotation result indicated that these SNPs may contribute to the development of lung cancer by affecting the availability of transcription factor binding sites. The HaploReg analysis suggested that rs9309336 may affect binding motif of transcription factor Foxp1. Expression quantitative trait loci analysis revealed that rs9309336 and rs17160062 could regulate the expressions of cancer-related genes (PUS10 and CHD1L). Our results revealed that variants in chromatin interaction regions could contribute to the development of lung cancer by regulating the expression of target genes, which providing novel implications for the understanding of functional variants in the development of lung cancer.

18.
Talanta ; 208: 120402, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816739

RESUMO

The main therapies of hepatocellular carcinoma (HCC) are hepatectomy and liver transplantation, but the recurrence rate of HCC after radical resection remains high. We established a novel method based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) for the rapid identification of four cancer stem cell-specific biomarkers to estimate the potential risk of HCC metastasis. After optimizing the final concentrations of Mg2+ and betaine, the sensitivity limits for detection of CK19 and EpCAM could reach 10 to 20 copies, while the sensitivity limits for the detection of CD133 and CD90 could reach 10 copies. We detected clinical specimens from 10 HCC patients and performed analysis before and after receiving hepatectomy using RT-LAMP and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results of both were consistent, but RT-LAMP was proved to be a more rapid, more sensitive, and more economic approach. This novel method is expected to estimate the recurrence and metastasis of HCC for clinical application by combining various low-cost circulating tumor cell sorting and detection tools.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Transcrição Reversa , Temperatura , Linhagem Celular Tumoral , Estudos de Viabilidade , Humanos , Metástase Neoplásica , Recidiva , Fatores de Tempo
19.
Environ Geochem Health ; 42(3): 769-780, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30852732

RESUMO

In recent years, acid rain had a serious negative impact on the leaching behavior of industrial waste residue. Researches were mainly focused on the environmental hazards of heavy metal in the leachate, but ignored the effects of heavy metal speciation on the stability of waste residue in the subsequent stabilization process. In this study, the unstable calcium-arsenic compounds in the arsenic calcium residue were firstly removed by leaching process; subsequently, the crystallization agent was added to treat the remaining calcium-arsenic mixture. The results of the leaching process demonstrated that the decrease in particle size and pH value directly affected the increase in the cumulative leaching amount of arsenic, and the cumulative leaching ratio reached 1.55%. In addition, the concentration of arsenic decreased from 3583 to 49.1 mg L-1. After the crystallization process, the arsenic concentration was lower than the limit value of Identification Standards for Hazardous Wastes (GB 5085.3-2007). The SEM analysis showed the bulk structures, and XRD pattern confirmed that they were the stable compounds. Moreover, the result of XRD and SEM illustrated that acid concentration, chloride ions and sulfate ions were contributed to the transformation and growth of stable calcium arsenate compounds. Therefore, effective control of the acidity of acid rain, the type of anions in acid rain, and the particle size of residues would contribute to adjusting the arsenic speciation to be more stable. The leaching-crystallization process was of great significance to improve the stability of the arsenic-containing residue.


Assuntos
Chuva Ácida , Arseniatos/química , Arsênico/química , Compostos de Cálcio/química , Chuva Ácida/análise , Arsênico/análise , Cálcio/análise , Cálcio/química , Cristalização , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Difração de Raios X
20.
Cancer Med ; 8(16): 6933-6944, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31566899

RESUMO

BACKGROUND: Portal vein tumor thrombus (PVTT) is a common complication in hepatocellular carcinoma (HCC), signaling dismal outcomes. This study was conducted to evaluate the survival benefit of postoperative portal vein perfusion chemotherapy (PVC) in patients with HCC and PVTT. METHODS: A retrospective review was conducted in 401 consecutive patients with HCC and PVTT who underwent hepatic resection between January 2009 and December 2015 and 67 patients received adjuvant postoperative PVC. A propensity score matching (PSM) was used to match patients with and without PVC at a ratio of 1:1. RESULTS: After PSM, the median time to recurrence (TTR) and overall survival (OS) were significantly longer in PVC group compared with control group (12.3 vs 5.8 months, P = .001; 19.0 vs 13.4 months, P = .037; respectively). At 1, 2, 3, and 5 years, the cumulative recurrence rates in PVC group were 48.1%, 86.5%, 92.3% ,96.2%, respectively, with OS rates of 63.8%, 37.9%, 24.4%, 18.3%, respectively; whereas cumulative recurrence rates of 76.6%, 91.5%, 94.3%, and 97.2%, respectively and OS rates of 55.4%, 23.0%, 12.4%, and 12.4%, respectively were recorded for the control group. In multivariate analysis, postoperative PVC emerged as a significant predictor for TTR (hazard ratio [HR], 0.523; P = .001) and OS (HR, 0.591; P = .010). PVC could reduce early recurrence (≤1 year) rate after surgical resection (40.3% vs 64.2%, P = .006) and clinical outcomes were further enhanced by adding sorafenib to postoperative PVC. CONCLUSIONS: Compared with surgical resection alone, postoperative adjuvant PVC treatment boosts survival and reduces early tumor recurrences in patients surgically treated for HCC and PVTT.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Trombose Venosa/tratamento farmacológico , Trombose Venosa/cirurgia , Carcinoma Hepatocelular/mortalidade , Feminino , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Perfusão , Veia Porta , Pontuação de Propensão , Trombectomia
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