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1.
Int J Mol Sci ; 24(17)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37686350

RESUMO

Aberrant mucus secretion is a hallmark of chronic obstructive pulmonary disease (COPD). Expression of the membrane-tethered mucins 3A and 3B (MUC3A, MUC3B) in human lung is largely unknown. In this observational cross-sectional study, we recruited subjects 45-65 years old from the general population of Stockholm, Sweden, during the years 2007-2011. Bronchial mucosal biopsies, bronchial brushings, and bronchoalveolar lavage fluid (BALF) were retrieved from COPD patients (n = 38), healthy never-smokers (n = 40), and smokers with normal lung function (n = 40). Protein expression of MUC3A and MUC3B in bronchial mucosal biopsies was assessed by immunohistochemical staining. In a subgroup of subjects (n = 28), MUC3A and MUC3B mRNAs were quantified in bronchial brushings using microarray. Non-parametric tests were used to perform correlation and group comparison analyses. A value of p < 0.05 was considered statistically significant. MUC3A and MUC3B immunohistochemical expression was localized to ciliated cells. MUC3B was also expressed in basal cells. MUC3A and MUC3B immunohistochemical expression was equal in all study groups but subjects with emphysema had higher MUC3A expression, compared to those without emphysema. Smokers had higher mRNA levels of MUC3A and MUC3B than non-smokers. MUC3A and MUC3B mRNA were higher in male subjects and correlated negatively with expiratory air flows. MUC3B mRNA correlated positively with total cell concentration and macrophage percentage, and negatively with CD4/CD8 T cell ratio in BALF. We concluded that MUC3A and MUC3B in large airways may be a marker of disease or may play a role in the pathophysiology of airway obstruction.


Assuntos
Enfisema , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Epitélio , Tórax , Doença Pulmonar Obstrutiva Crônica/genética , Mucinas/genética
2.
Mol Cell Probes ; 71: 101920, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37442529

RESUMO

BACKGROUND: Aberrant expression of circRNAs is involved in the progression of hepatocellular carcinoma (HCC). This study aimed at screening the pro-tumorigenic circular RNAs (circRNAs) in HCC and the mechanisms of circCPSF6 expression influencing HCC characteristics. METHOD: circCPSF6 was identified in HCC tissues using high-throughput sequencing data, and its expression was verified in both HCC tissues and cell lines using quantitative real-time PCR (qRT-PCR). CCK-8 and Transwell assays were used to evaluate the effects of circCPSF6 on HCC proliferation and migration. A xenograft mouse model was used to investigate the effects of circCPSF6 on HCC progression in vivo, and the significance of circCPSF6 in HCC was verified both in vivo and in vitro. circCPSF6-associated miRNAs and mRNAs were identified using bioinformatic analyses. Luciferase reporter, RNA pull-down, Fluorescence in situ hybridization, and RNA immunoprecipitation assays were performed to elucidate the circCPSF6 regulatory axis in HCC. RESULT: CircCPSF6 expression was increased in HCC cell lines and tissues, and the expression of its parental mRNA was positively correlated with tumor severity and negatively correlated with survival. Mechanistic analyses of HCC cell lines showed that tumorigenesis was inhibited by circCPSF6 knockdown and promoted by its overexpression. Functional analyses revealed that circCPSF6 mediated HCC development by sponging miR-145-5p as a competing endogenous RNA. Furthermore, this sponging upregulated the miR-145-5p target gene MAP4K4, a classical pro-tumorigenic gene. CONCLUSION: Our findings reveal a regulatory network that includes the circCPSF6-miR-145-5p-MAP4K4 axis. Elements of this axis are potential HCC biomarkers, as well as targets for HCC treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , RNA Circular/genética , Hibridização in Situ Fluorescente , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Serina-Treonina Quinases/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética
3.
Brief Bioinform ; 25(1)2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-38205966

RESUMO

Multi-omics data integration is a complex and challenging task in biomedical research. Consensus clustering, also known as meta-clustering or cluster ensembles, has become an increasingly popular downstream tool for phenotyping and endotyping using multiple omics and clinical data. However, current consensus clustering methods typically rely on ensembling clustering outputs with similar sample coverages (mathematical replicates), which may not reflect real-world data with varying sample coverages (biological replicates). To address this issue, we propose a new consensus clustering with missing labels (ccml) strategy termed ccml, an R protocol for two-step consensus clustering that can handle unequal missing labels (i.e. multiple predictive labels with different sample coverages). Initially, the regular consensus weights are adjusted (normalized) by sample coverage, then a regular consensus clustering is performed to predict the optimal final cluster. We applied the ccml method to predict molecularly distinct groups based on 9-omics integration in the Karolinska COSMIC cohort, which investigates chronic obstructive pulmonary disease, and 24-omics handprint integrative subgrouping of adult asthma patients of the U-BIOPRED cohort. We propose ccml as a downstream toolkit for multi-omics integration analysis algorithms such as Similarity Network Fusion and robust clustering of clinical data to overcome the limitations posed by missing data, which is inevitable in human cohorts consisting of multiple data modalities. The ccml tool is available in the R language (https://CRAN.R-project.org/package=ccml, https://github.com/pulmonomics-lab/ccml, or https://github.com/ZhoulabCPH/ccml).


Assuntos
Asma , Multiômica , Adulto , Humanos , Consenso , Análise por Conglomerados , Algoritmos , Asma/genética
4.
Brief Bioinform ; 25(1)2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-38221905

RESUMO

BACKGROUND: Portal vein thrombosis (PVT) is a significant issue in cirrhotic patients, necessitating early detection. This study aims to develop a data-driven predictive model for PVT diagnosis in chronic hepatitis liver cirrhosis patients. METHODS: We employed data from a total of 816 chronic cirrhosis patients with PVT, divided into the Lanzhou cohort (n = 468) for training and the Jilin cohort (n = 348) for validation. This dataset encompassed a wide range of variables, including general characteristics, blood parameters, ultrasonography findings and cirrhosis grading. To build our predictive model, we employed a sophisticated stacking approach, which included Support Vector Machine (SVM), Naïve Bayes and Quadratic Discriminant Analysis (QDA). RESULTS: In the Lanzhou cohort, SVM and Naïve Bayes classifiers effectively classified PVT cases from non-PVT cases, among the top features of which seven were shared: Portal Velocity (PV), Prothrombin Time (PT), Portal Vein Diameter (PVD), Prothrombin Time Activity (PTA), Activated Partial Thromboplastin Time (APTT), age and Child-Pugh score (CPS). The QDA model, trained based on the seven shared features on the Lanzhou cohort and validated on the Jilin cohort, demonstrated significant differentiation between PVT and non-PVT cases (AUROC = 0.73 and AUROC = 0.86, respectively). Subsequently, comparative analysis showed that our QDA model outperformed several other machine learning methods. CONCLUSION: Our study presents a comprehensive data-driven model for PVT diagnosis in cirrhotic patients, enhancing clinical decision-making. The SVM-Naïve Bayes-QDA model offers a precise approach to managing PVT in this population.


Assuntos
Veia Porta , Trombose Venosa , Humanos , Veia Porta/patologia , Fatores de Risco , Teorema de Bayes , Medicina de Precisão , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Fibrose , Trombose Venosa/complicações , Trombose Venosa/diagnóstico
5.
Front Genet ; 13: 1010048, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36468026

RESUMO

Rationale: Chronic obstructive pulmonary disease (COPD) is a complex disease caused by a multitude of underlying mechanisms, and molecular mechanistic modeling of COPD, especially at a multi-molecular level, is needed to facilitate the development of molecular diagnostic and prognostic tools and efficacious treatments. Objectives: To investigate the miRNA-mRNA-protein dysregulated network to facilitate prediction of biomarkers and disease subnetwork in COPD in women. Measurements and Results: Three omics data blocks (mRNA, miRNA, and protein) collected from BAL cells from female current-smoker COPD patients, smokers with normal lung function, and healthy never-smokers were integrated with miRNA-mRNA-protein regulatory networks to construct a COPD-specific dysregulated network. Furthermore, downstream network topology, literature annotation, and functional enrichment analysis identified both known and novel disease-related biomarkers and pathways. Both abnormal regulations in miRNA-induced mRNA transcription and protein translation repression play roles in COPD. Finally, the let-7-AIFM1-FKBP1A pathway is highlighted in COPD pathology. Conclusion: For the first time, a comprehensive miRNA-mRNA-protein dysregulated network of primary immune cells from the lung related to COPD in females was constructed to elucidate specific biomarkers and disease pathways. The multi-omics network provides a new molecular insight from a multi-molecular aspect and highlights dysregulated interactions. The highlighted let-7-AIFM1-FKBP1A pathway also indicates new hypotheses of COPD pathology.

6.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34864875

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly became a global health challenge, leading to unprecedented social and economic consequences. The mechanisms behind the pathogenesis of SARS-CoV-2 are both unique and complex. Omics-scale studies are emerging rapidly and offer a tremendous potential to unravel the puzzle of SARS-CoV-2 pathobiology, as well as moving forward with diagnostics, potential drug targets, risk stratification, therapeutic responses, vaccine development and therapeutic innovation. This review summarizes various aspects of understanding multiomics integration-based molecular characterizations of COVID-19, which to date include the integration of transcriptomics, proteomics, genomics, lipidomics, immunomics and metabolomics to explore virus targets and developing suitable therapeutic solutions through systems biology tools. Furthermore, this review also covers an abridgment of omics investigations related to disease pathogenesis and virulence, the role of host genetic variation and a broad array of immune and inflammatory phenotypes contributing to understanding COVID-19 traits. Insights into this review, which combines existing strategies and multiomics integration profiling, may help further advance our knowledge of COVID-19.


Assuntos
COVID-19 , Genômica , Pandemias , SARS-CoV-2 , Biologia de Sistemas , COVID-19/epidemiologia , COVID-19/genética , COVID-19/metabolismo , Humanos , SARS-CoV-2/genética , SARS-CoV-2/metabolismo
8.
Respir Res ; 22(1): 40, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546682

RESUMO

BACKGROUND: Observational data under real-life conditions in idiopathic pulmonary fibrosis (IPF) is scarce. We explored anti-fibrotic treatment, disease severity and phenotypes in patients with IPF from the Swedish IPF Registry (SIPFR). METHODS: Patients enrolled between September 2014 and April 2020 and followed ≥ 6 months were investigated. Demographics, comorbidities, lung function, composite variables, six-minute walking test (6MWT), quality of life, and anti-fibrotic therapy were evaluated. Agreements between classification of mild physiological impairment (defined as gender-age-physiology (GAP) stage 1) with physiological and composite measures of severity was assessed using kappa values and their impact on mortality with hazard ratios. The factor analysis and the two-step cluster analysis were used to identify phenotypes. Univariate and multivariable survival analyses were performed between variables or groups. RESULTS: Among 662 patients with baseline data (median age 72.7 years, 74.0% males), 480 had a follow up ≥ 6 months with a 5 year survival rate of 48%. Lung function, 6MWT, age, and BMI were predictors of survival. Patients who received anti-fibrotic treatment ≥ 6 months had better survival compared to untreated patients [p = 0.007, HR (95% CI): 1.797 (1.173-2.753)] after adjustment of age, gender, BMI, smoking status, forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO). Patients with mild physiological impairment (GAP stage 1, composite physiological index (CPI) ≤ 45, DLCO ≥ 55%, FVC ≥ 75%, and total lung capacity (TLC) ≥ 65%, respectively) had better survival, after adjustment for age, gender, BMI and smoking status and treatment. Patients in cluster 1 had the worst survival and consisted mainly of male patients with moderate-severe disease and an increased prevalence of heart diseases at baseline; Cluster 2 was characterized by mild disease with more than 50% females and few comorbidities, and had the best survival; Cluster 3 were younger, with moderate-severe disease and had few comorbidities. CONCLUSION: Disease severity, phenotypes, and anti-fibrotic treatment are closely associated with the outcome in IPF, with treated patients surviving longer. Phenotypes may contribute to predicting outcomes of patients with IPF and suggest the patients' need for special management, whereas single or composite variables have some limitations as disease predictors.


Assuntos
Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/mortalidade , Sistema de Registros , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Feminino , Seguimentos , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/administração & dosagem , Taxa de Sobrevida/tendências , Suécia/epidemiologia , Capacidade Vital/efeitos dos fármacos , Capacidade Vital/fisiologia
9.
Int J Med Sci ; 18(5): 1185-1188, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33526979

RESUMO

Background: Increased stress among medical personnel had been reported in previous virus outbreaks. The novel coronavirus disease (COVID-19) emerged in December 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). No qualitative assessment has yet described the physical and mental health conditions of frontline medical personnel in the COVID-19 outbreaks. Methods: Here, 251 frontline medical personnel involved in COVID-19 missions completed electronic questionnaires, consisting of 31 categorical variables related to their physical and mental health status, medical history and environmental conditions. We constructed a correlation amongst these variables through pairwise Kendall rank correlation coefficient test. Then, clusters of highly correlated variables were identified using the leading eigenvector. Finally, we used the network and clusters to clarify the correlations amongst variables. Results: This qualitative study identified the six clusters. Cluster 1 was characterized by skin allergy. Cluster 2 was predominantly associated with anxiety. Cluster 3 consisted mostly of respiratory symptoms. The participants in cluster 4 had medical history. Cluster 5 and cluster 6 were characterized by disinfection and demography, respectively. Finally, we revealed three major findings. First, more than 80% of medical personnel worry about COVID-19-related infection and experience newly appearing anxiety (56.2%), airway or heart symptoms (34.3%) and skin allergies (20.3%). Second, COVID-19-related worry significantly associates with all variables in the anxiety and respiratory symptom clusters. Third, new-onset skin allergies did not associate with either disinfection or anxiety, but did associate with a previous history of allergies. Conclusions: COVID-19-related worry leads to physical and mental health problems amongst medical personnel. Effective responses and interventions could relieve a series of new-onset physical and mental health problems.


Assuntos
COVID-19 , Surtos de Doenças , Pessoal de Saúde/psicologia , Adulto , COVID-19/epidemiologia , China/epidemiologia , Análise por Conglomerados , Feminino , Nível de Saúde , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Adulto Jovem
10.
JCI Insight ; 6(2)2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33290275

RESUMO

The pathogenesis of chronic obstructive pulmonary disease (COPD) involves aberrant responses to cellular stress caused by chronic cigarette smoke (CS) exposure. However, not all smokers develop COPD and the critical mechanisms that regulate cellular stress responses to increase COPD susceptibility are not understood. Because microRNAs are well-known regulators of cellular stress responses, we evaluated microRNA expression arrays performed on distal parenchymal lung tissue samples from 172 subjects with and without COPD. We identified miR-24-3p as the microRNA that best correlated with radiographic emphysema and validated this finding in multiple cohorts. In a CS exposure mouse model, inhibition of miR-24-3p increased susceptibility to apoptosis, including alveolar type II epithelial cell apoptosis, and emphysema severity. In lung epithelial cells, miR-24-3p suppressed apoptosis through the BH3-only protein BIM and suppressed homology-directed DNA repair and the DNA repair protein BRCA1. Finally, we found BIM and BRCA1 were increased in COPD lung tissue, and BIM and BRCA1 expression inversely correlated with miR-24-3p. We concluded that miR-24-3p, a regulator of the cellular response to DNA damage, is decreased in COPD, and decreased miR-24-3p increases susceptibility to emphysema through increased BIM and apoptosis.


Assuntos
Apoptose/genética , Dano ao DNA/genética , MicroRNAs/genética , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Animais , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Proteína 11 Semelhante a Bcl-2/genética , Proteína 11 Semelhante a Bcl-2/metabolismo , Linhagem Celular , Fumar Cigarros/efeitos adversos , Estudos de Coortes , Reparo do DNA , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Humanos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos AKR , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma
11.
Respir Res ; 21(1): 239, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948202

RESUMO

RATIONALE: Smoking-related chronic obstructive pulmonary disease (COPD) is associated with dysregulated production of mucus. Mucins (MUC) are important both for mucus secretion and epithelial defense. We have examined the distribution of MUC1 and MUC4 in the airway epithelial cells of never-smokers and smokers with and without COPD. METHODS: Mucosal biopsies and bronchial wash samples were obtained by bronchoscopy from age- and sex-matched COPD-patients (n = 38; GOLD I-II/A-B), healthy never-smokers (n = 40) and current smokers with normal lung function (n = 40) from the Karolinska COSMIC cohort (NCT02627872). Cell-specific expressions of MUC1, MUC4 and regulating factors, i.e., epithelial growth factor receptor (EGFR) 1 and 2, were analyzed by immunohistochemistry. Soluble MUC1 was measured by quantitative immunodetection on slot blot. RESULTS: The levels of cell-bound MUC1 expression in basal cells and in soluble MUC1 in bronchial wash were increased in smokers, regardless of airway obstruction. Patients with chronic bronchitis had higher MUC1 expression. The expression of MUC4 in cells with goblet cell phenotype was increased in smokers. The expression of EGFR2, but not that of EGFR1, was higher in never-smokers than in smokers. CONCLUSIONS: Smoking history and the presence of chronic bronchitis, regardless of airway obstruction, affect both cellular and soluble MUC1 in human airways. Therefore, MUC1 may be a novel marker for smoking- associated airway disease.


Assuntos
Broncoscopia/métodos , Mucina-1/biossíntese , Mucina-4/biossíntese , Mucosa Respiratória/metabolismo , Fumar/metabolismo , Idoso , Bronquite/diagnóstico , Bronquite/epidemiologia , Bronquite/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Mucosa Respiratória/patologia , Fumar/efeitos adversos , Fumar/epidemiologia
12.
Int J Chron Obstruct Pulmon Dis ; 15: 1049-1059, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32546996

RESUMO

Introduction: The vitamin D binding protein (VDBP, also known as GC-globulin) and vitamin D deficiency have been associated with chronic obstructive pulmonary disease (COPD). rs7041 and rs4588 are two single nucleotide polymorphisms of the VDBP gene, including three common allelic variants (GC1S, GC1F and GC2). Previous studies primarily assessed the serum levels of vitamin D and VDBP in COPD. However, less is known regarding the impact of the local release of VDBP on COPD lung function. Thus, we examined the association of sputum and plasma VDBP with lung function at baseline and at four years, and examined potential genetic polymorphism interactions. Methods: The baseline levels of sputum VDBP, plasma VDBP and plasma 25-OH vitamin D, as well as the GC rs4588 and rs7041 genotypes, were assessed in a 4-year Finnish follow-up cohort (n = 233) of non-smokers, and smokers with and without COPD. The associations between the VDBP levels and the longitudinal decline of lung function were further analysed. Results: High frequencies of the haplotypes in rs7041/rs4588 were homozygous GC1S/1S (42.5%). Higher sputum VDBP levels in stage I and stage II COPD were observed only in carriers with GC1S/1S genotype when compared with non-smokers (p = 0.034 and p = 0.002, respectively). Genotype multivariate regression analysis indicated that the baseline sputum VDBP and FEV1/FVC ratio at baseline independently predicted FEV1% at follow-up. Discussion and Conclusion: The baseline sputum VDBP expression was elevated in smokers with COPD among individuals with the GC1S/1S genotype, and predicted follow-up airway obstruction. Our results suggest that the GC polymorphism should be considered when exploring the potential of VDBP as a biomarker for COPD.


Assuntos
Obstrução das Vias Respiratórias , Doença Pulmonar Obstrutiva Crônica , Fumantes , Proteína de Ligação a Vitamina D , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética , Escarro , Vitamina D , Proteína de Ligação a Vitamina D/genética
13.
Respir Res ; 21(1): 96, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321530

RESUMO

The novel coronavirus disease (COVID-19) outbreak started in December 2019 in Wuhan, China, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The CT image is used to assess the disease progress, whereas the continued two times of negative results from SARS-CoV-2 nucleic acid detection had been considered as a criterion for ending antiviral treatment. We compared the two COVID-19 cases with similar backgrounds and CT image repeated intervals under treatment. Our report highlighted the unsynchronized expression in the changes of CT image and nucleic acid detection in COVID-19, and lasting positive nucleic acid test result in patients recovered from pneumonia. It may be contributed to recognize the disease and improve prevention.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/diagnóstico , RNA Viral/isolamento & purificação , Tomografia Computadorizada por Raios X , Adulto , Betacoronavirus , COVID-19 , Teste para COVID-19 , China , Técnicas de Laboratório Clínico , Infecções por Coronavirus/tratamento farmacológico , Humanos , Pulmão/diagnóstico por imagem , Pulmão/virologia , Masculino , Pandemias , Pneumonia Viral/tratamento farmacológico , SARS-CoV-2 , Carga Viral
14.
Eur Respir J ; 51(5)2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29545283

RESUMO

Chronic obstructive pulmonary disease (COPD) is an umbrella diagnosis caused by a multitude of underlying mechanisms, and molecular sub-phenotyping is needed to develop molecular diagnostic/prognostic tools and efficacious treatments.The objective of these studies was to investigate whether multi-omics integration improves the accuracy of molecular classification of COPD in small cohorts.Nine omics data blocks (comprising mRNA, micro RNA, proteomes and metabolomes) collected from several anatomical locations from 52 female subjects were integrated by similarity network fusion (SNF). Multi-omics integration significantly improved the accuracy of group classification of COPD patients from healthy never-smokers and from smokers with normal spirometry, reducing required group sizes from n=30 to n=6 at 95% power. Seven different combinations of four to seven omics platforms achieved >95% accuracy.For the first time, a quantitative relationship between multi-omics data integration and accuracy of data-driven classification power has been demonstrated across nine omics data blocks. Integrating five to seven omics data blocks enabled 100% correct classification of COPD diagnosis with groups as small as n=6 individuals, despite strong confounding effects of current smoking. These results can serve as guidelines for the design of future systems-based multi-omics investigations, with indications that integrating five to six data blocks from several molecular levels and anatomical locations suffices to facilitate unsupervised molecular classification in small cohorts.


Assuntos
Metaboloma , Proteoma , Proteômica , Doença Pulmonar Obstrutiva Crônica , Fumar , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Variação Biológica da População , Líquido da Lavagem Broncoalveolar , Estudos Transversais , Confiabilidade dos Dados , Feminino , Humanos , MicroRNAs/análise , Pessoa de Meia-Idade , não Fumantes/estatística & dados numéricos , Proteômica/métodos , Proteômica/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/classificação , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Testes de Função Respiratória , Fumantes/estatística & dados numéricos , Fumar/metabolismo , Fumar/patologia , Suécia
15.
World J Hepatol ; 7(20): 2309-14, 2015 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-26380655

RESUMO

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and is the third leading cause of cancer-related death. Liver transplantation (LT) has become a curative treatment for patients with HCC. However, recurrence and metastasis after LT are the main factors reducing long-term survival in patients, and the lung is the most common site of metastasis after LT for HCC, although metastasis to liver, para-aortic lymph nodes and renal periphery are observed. Thus, the treatment of pulmonary metastases after LT for HCC has become a hot research topic, the successful treatment of pulmonary metastases can significantly prolong the survival of LT patients. Although single conventional treatment (chemotherapy, surgery and external beam radiation therapy), immunosuppression, image-guided minimally invasive therapy (radiofrequency ablation, microwave ablation, cryoablation, and brachytherapy) and molecular targeted drugs have had a significant effect, patients do not have durable remission and the long-term survival rate is disappointing. Therefore, improving existing treatments and identifying a more effective combination therapy are important research issues in the prevention and treatment of pulmonary metastases after LT for HCC. The paper reviewed single conventional treatments, new treatments, and combination therapy, to provide a basis for the best treatment of these patients.

16.
Ying Yong Sheng Tai Xue Bao ; 26(9): 2707-13, 2015 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-26785552

RESUMO

Taking winter wheat cultivar 'Tainong 18' as test material, this paper set three treatments, local farmer's traditional cultivation pattern (FP), super high yield pattern (SH) and high yield high efficiency pattern ( HH) to investigate the effects of cultivation patterns on the intercepted photosynthetically active radiation (IPAR), PAR use efficiency (RUE), dry matter (DM) accumulation, harvest index (HI), grain yield and fertilizers' partial factor productivity (PFP) in 2012-2013. The results showed that IPAR, RUE and DM accumulation of the total growth stage and grain yield under SH pattern were significantly higher than those under FP pattern. IPAR of the total growth stage under HH pattern was lower than that under FP pattern, but RUE, DM accumulation and HI were significantly higher than that under FP pattern, so grain yield was higher than that under FP pattern. The grain yields under HH pattern were respectively decreased by 3.8% and 2.8% under high and low fertility levels compared that under SH pattern, while the PFP of N, P and K under HH pattern were averagely 26.4%, 68.5% and 92.6% higher than those under SH pattern, respectively. In conclusion, HH pattern, with the characteristics of 'reducing fertilizer', 'increasing planting density' and 'delaying sowing date', was the recommended cultivation pattern under the condition similar to this experiment balancing the grain yield, radiation use and fertilizer use.


Assuntos
Agricultura/métodos , Radiação , Triticum/crescimento & desenvolvimento , Triticum/efeitos da radiação , Fertilizantes , Fotossíntese
17.
World J Gastroenterol ; 19(23): 3649-57, 2013 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-23801868

RESUMO

AIM: To analyze the prognostic factors of 5-year survival and 10-year survival in hepatocellular carcinoma (HCC) patients, and to explore the reasons for long-term survival and provide choice of treatment modalities for HCC patients. METHODS: From January 1990 to October 2012, 8450 HCC patients were included in a prospective database compiled by the Information Center after hospital admission. Long-term surviving patients were included in a 10-year survival group (520 patients) and a 5-year survival group (1516 patients) for analysis.The long-term survival of HCC patients was defined as the survival of 5 years or longer. Clinical and biologic variables were assessed using univariate and multivariate analyses. The survival of patients was evaluated by follow-up data. RESULTS: The long-term survival of HCC patients was associated with the number of lesions, liver cirrhosis and Child-Pugh classification. It was not found to be associated with tumor diameter, histological stage, and pretreatment level of serum α-fetoprotein. The differences in clinical factors between the 5-year survival and the 10-year survival were found to be the number of lesions, liver cirrhosis, Child-Pugh classification, and time elapsed until first recurrence or metastasis. The survival period of different treatment modalities in the patients who survived for 5 years and 10 years showed significant differences: (in order of significance) surgery alone > surgery-transcatheter arterial chemoembolization (TACE) > TACE-radiofrequency ablation (RFA) > TACE alone > surgery-TACE-RFA. The 10-year survival of HCC patients was not associated with the choice of treatment modality. CONCLUSION: This retrospective study elucidated survival outcomes, prognostic factors affecting survival and treatment modalities in HCC patients.


Assuntos
Carcinoma Hepatocelular/terapia , Ablação por Cateter , Quimioembolização Terapêutica , Hepatectomia , Neoplasias Hepáticas/terapia , Sobreviventes , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Distribuição de Qui-Quadrado , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
18.
FEBS Lett ; 587(7): 976-82, 2013 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-23454638

RESUMO

The genomic architecture of several functional elements in animals and plants, such as microRNAs and tRNA, has been better characterized. As yet, there is very little known about genomic organization and structure of lncRNA in animals and plants. Here, we conducted a genome-wide systematic computational analysis of genomic architecture of lncRNAs, and further provided a more comprehensive comparative view of genomic organization between lncRNAs and several other functional elements in the human genome. Our study not only provides comprehensive knowledge for further studies into the correlations between the genomic architecture of lncRNAs and their important functional roles in diverse cellular processes and in disease, but also will be valuable for understanding the origin and evolution of lncRNAs.


Assuntos
Biologia Computacional/métodos , Genoma Humano/genética , Genômica/métodos , RNA Longo não Codificante/genética , Algoritmos , Fragilidade Cromossômica/genética , Mapeamento Cromossômico , Evolução Molecular , Humanos , Sequências Repetitivas de Ácido Nucleico/genética
19.
Zhonghua Yi Xue Za Zhi ; 92(9): 596-9, 2012 Mar 06.
Artigo em Chinês | MEDLINE | ID: mdl-22800946

RESUMO

OBJECTIVE: To study the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) features of VX2 rabbits carcinoma metastatic and inflammatory lymph nodes. METHODS: Twenty healthy adult New-Zealand white rabbits were divided into metastatic lymph node group and inflammatory lymph node group randomly. There were ten rabbits in each group. All 20 rabbits underwent DCE-MRI. Peak enhancement, time to peak, maximum slope and signal intensity versus time curves were generated from each node individually. RESULTS: DCE-MRI were obtained for nine cases of metastatic lymph nodes and nine cases of inflammatory lymph nodes. The signal intensity versus time curves of metastatic lymph nodes were appeared as rapid ascending and plateauing, and peak enhancement, time to peak, maximum slope of metastatic lymph nodes group were 284% ± 125%, (118 ± 47) s and (6.5 ± 2.7)%/s, respectively. The signal intensity versus time curves of inflammatory lymph nodes were appeared as insisting ascending, and peak enhancement, time to peak, maximum slope of inflammatory lymph nodes group were 199% ± 109%, (143 ± 40) s and (3.6 ± 1.5)%/s, respectively. There was significantly higher peak enhancement, shorter time to peak and higher maximum slope in the metastatic lymph nodes group compared with the inflammatory lymph nodes group (P < 0.05). CONCLUSIONS: DCE-MRI can accurately reflect the hemodynamic characteristics of VX2 rabbits neoplasm metastatic lymph nodes and inflammatory lymph nodes, and can differentiate VX2 rabbits neoplasm metastatic lymph nodes from inflammatory lymph nodes.


Assuntos
Metástase Linfática/patologia , Imageamento por Ressonância Magnética/métodos , Pseudolinfoma/patologia , Animais , Aumento da Imagem , Inflamação , Linfonodos/patologia , Linfadenite/diagnóstico , Linfadenite/patologia , Metástase Linfática/diagnóstico , Pseudolinfoma/diagnóstico , Coelhos
20.
Chin Med J (Engl) ; 124(20): 3386-93, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22088540

RESUMO

BACKGROUND: Imaging-guided thermal ablation using different energy sources continues to gain favor as a minimally invasive technique for the treatment of primary and metastatic hepatic malignant tumors. This study aimed to evaluate the performance of microwave ablation with 2450-MHz internally cooled-shaft antenna in ex vivo and in vivo porcine livers. METHODS: All studies were animal care and ethics committee approved. Microwave ablation was performed using a noncooled or cooled-shaft antenna in 23 ex vivo (92 ablations) and eight in vivo (36 ablations) porcine livers. Diameters of the coagulation zone were observed on gross specimens. The coagulation diameters achieved in different microwave ablation parameter groups were compared. Curve estimation analysis was performed to characterize the relationship between applied power and treatment duration and coagulation diameter (including short-axis and long-axis diameter). RESULTS: Coagulation zones were elliptical and an arrowed-shaped carbonization zone around the shaft was observed in all groups. But the antenna track was also coagulated in the noncooled-shaft antenna groups. In ex vivo livers, the short-axis diameter correlated with the power output in a quadratic curve fashion (R(2) = 0.95) by fixing ablation duration to 10 minutes, and correlated with the ablation duration in a logarithmic curve fashion (R(2) = 0.98) by fixing power output to 80 W. The short-axis reached a relative plateau within 25 minutes. In in vivo livers, short-axis diameter correlated with the coagulation duration in a sigmoidal curve fashion (60 W group R(2) = 0.76, 80 W group R(2) = 0.87), with a relative plateau achieved within 10 minutes for power settings of 60 W and 80 W. CONCLUSIONS: The internally cooled microwave antenna may be advantageous to minimize collateral damage. The short-axis diameter enlargement has a plateau by fixing power output.


Assuntos
Ablação por Cateter , Micro-Ondas , Animais , Fígado/cirurgia , Suínos
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