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1.
Plant Dis ; : PDIS08191722RE, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31999220

RESUMO

The gray mold caused by Botrytis cinerea has a significant impact on tomato production throughout the world. Although the synthetic fungicide fludioxonil can effectively control B. cinerea, there have been several reports of resistance to this fungicide. This study indicated that all of the fludioxonil-resistant strains tested, including one field-resistant isolate and four laboratory strains, had reduced fitness relative to sensitive isolates. In addition to having reduced growth, sporulation, and pathogenicity, the resistant strains were more sensitive to osmotic stress and had significantly (P < 0.05) higher peroxidase activity. BOs1, a kinase in the high-osmolarity glycerol stress response signal transduction pathway, is believed to harbor mutations related to fludioxonil resistance. Sequence analysis of their BOs1 sequences indicated that the fludioxonil-resistant field isolate, XXtom1806, had four point mutations resulting in four amino acid changes (I365S, S531G, T565N, and T1267A) and three amino acids (I365S, S531G, and T565N) in the histidine kinases, adenylyl cyclases, methyl-accepting chemotaxis receptors, and phosphatases domain, which associated with fludioxonil binding. Similarly, two of the laboratory strains, XXtom-Lab1 and XXtom-Lab4, had three (Q846S, I1126S, and G415D) and two (P1051S and V1241M) point mutations, respectively. A third strain, XXtom-lab3, had a 52-bp insertion that included a stop codon at amino acid 256. Interestingly, the BOs1 sequence of the fourth laboratory strain, XXtom-lab5, was identical to those of the sensitive isolates, indicating that an alternative resistance mechanism exists. The study also found evidence of positive cross-resistance between fludioxonil and the dicarboximide fungicides procymidone and iprodione, but no cross-resistance was detected with any other fungicides tested, including boscalid, carbendazim, tebuconazole, and fluazinam.

2.
Sci Rep ; 9(1): 18321, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797961

RESUMO

The novel methods for efficient plant regeneration via direct somatic embryogenesis (SE) and SE-mediated transformation system under high concentration of NAA in Ranunculus sceleratus were established. On MS media containing a high concentration of NAA (10.0 mg/L) in the dark, all inoculated explants (root, stem and leaf) formed somatic embryos at high frequencies, respectively, 66.03, 126.47 and 213.63 embryoids per explant, and 100% of the embryoids developed into plantlets on 1/2 MS rooting media. Morphological and histological analyses revealed that SE in R. sceleratus followed a classical pattern. All inoculated explants can be used as receptors for genetic transformation in R. sceleratus, through direct SE-mediated method after Agrobacterium infection. RcLEC1-B, as a marker gene, changed the number and morphology of flower organs and the development of cuticle in R. sceleratus, which indicated that the efficient transgenic system of R. sceleratus was established. To our knowledge, this is the first observation that both direct SE and transgenic transformation system, via induction of a single plant growth regulator, have been successfully constructed in R. sceleratus.

3.
Clin Respir J ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31758867

RESUMO

INTRODUCTION: The characteristics of Allergic Bronchopulmonary Aspergillosis (ABPA) based on its radiological classification is still unclear. OBJECTIVES: To investigate the clinical significances of ABPA patients with central bronchiectasis (ABPA-CB) by different radiological classifications of mucus plugs. METHODS: ABPA-CB patients from a pulmonary hospital between 2008 and 2015 were retrospectively included and analysed. According to the chest imaging in their first visit to physician, the ABPA-CB patients were divided into two groups based on the presence of high-attenuation mucus (HAM) or low-attenuation mucus (LAM). The primary endpoint was ABPA relapse within 1 year since the glucocorticoid withdrawal. The relationship between the imaging findings and the clinical prognosis was illuminated. RESULTS: A total of 125 ABPA patients were analysed in this study. Compared to the LAM group, the HAM group presented higher blood eosinophil cells counts, higher rates of Aspergillus detection isolated in sputum and expectoration of brownish-black mucus plugs, more affected lobes and segments, poorer pulmonary function and higher rate of relapse. CONCLUSIONS: The clinical characteristics and prognosis of ABPA-CB patients are closely related to its radiological phenotype of mucus plugs in the central bronchiectasis. Clinicians should promote a diversity of personalized treatments for different patients with different radiological characteristics.

4.
Regen Med ; 14(5): 359-387, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31204905

RESUMO

Aim: A systematic multimolecule drug design procedure is proposed for promoting hepatogenesis and liver regeneration. Materials & methods: Genome-wide microarray data including three hepatic conditions are obtained from the GEO database (GSE15238). System modeling and big data mining methods are used to construct real genome-wide genetic-and-epigenetic networks (GWGENs). Then, we extracted the core GWGENs by applying principal network projection on real GWGENs of normal, developing and regenerating livers, respectively. After that, we investigated the significant signal pathways and epigenetic modifications in the core GWGENs to identify potential biomarkers as drug targets. Result & conclusion: A multimolecule drug consisting of sulmazole, clofibrate, colchicine, furazolidone, nadolol, eticlopride and felbinac is proposed to target on novel biomarkers for promoting hepatogenesis and liver regeneration.

5.
Oncotarget ; 10(38): 3760-3806, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31217907

RESUMO

Non-small-cell lung cancer (NSCLC) is the predominant type of lung cancer in the world. Lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC) are subtypes of NSCLC. We usually regard them as different disease due to their unique molecular characteristics, distinct cells of origin and dissimilar clinical response. However, the differences of genetic and epigenetic progression mechanism between LADC and LSCC are complicated to analyze. Therefore, we applied systems biology approaches and big databases mining to construct genetic and epigenetic networks (GENs) with next-generation sequencing data of LADC and LSCC. In order to obtain the real GENs, system identification and system order detection are conducted on gene regulatory networks (GRNs) and protein-protein interaction networks (PPINs) for each stage of LADC and LSCC. The core GENs were extracted via principal network projection (PNP). Based on the ranking of projection values, we got the core pathways in respect of KEGG pathway. Compared with the core pathways, we found significant differences between microenvironments, dysregulations of miRNAs, epigenetic modifications on certain signaling transduction proteins and target genes in each stage of LADC and LSCC. Finally, we proposed six genetic and epigenetic multiple-molecule drugs to target essential biomarkers in each progression stage of LADC and LSCC, respectively.

6.
Int J Mol Sci ; 20(10)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126066

RESUMO

Thyroid cancer is the most common endocrine cancer. Particularly, papillary thyroid cancer (PTC) accounts for the highest proportion of thyroid cancer. Up to now, there are few researches discussing the pathogenesis and progression mechanisms of PTC from the viewpoint of systems biology approaches. In this study, first we constructed the candidate genetic and epigenetic network (GEN) consisting of candidate protein-protein interaction network (PPIN) and candidate gene regulatory network (GRN) by big database mining. Secondly, system identification and system order detection methods were applied to prune candidate GEN via next-generation sequencing (NGS) and DNA methylation profiles to obtain the real GEN. After that, we extracted core GENs from real GENs by the principal network projection (PNP) method. To investigate the pathogenic and progression mechanisms in each stage of PTC, core GEN was denoted in respect of KEGG pathways. Finally, by comparing two successive core signaling pathways of PTC, we not only shed light on the causes of PTC progression, but also identified essential biomarkers with specific gene expression signature. Moreover, based on the identified gene expression signature, we suggested potential candidate drugs to prevent the progression of PTC with querying Connectivity Map (CMap).


Assuntos
Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Metilação de DNA , Mineração de Dados , Progressão da Doença , Redes Reguladoras de Genes , Humanos , Biologia de Sistemas , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Transcriptoma
7.
Dis Markers ; 2018: 8635329, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30344796

RESUMO

The prevalence of hepatocellular carcinoma (HCC) is still high worldwide because liver diseases could develop into HCC. Recent reports indicate nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NAFLD&NASH) and primary biliary cirrhosis and primary sclerosing cholangitis (PBC&PSC) are significant of HCC. Therefore, understanding the cellular mechanisms of the pathogenesis and hepatocarcinogenesis from normal liver cells to HCC through NAFLD&NASH or PBC&PSC is a priority to prevent the progression of liver damage and reduce the risk of further complications. By the genetic and epigenetic data mining and the system identification through next-generation sequencing data and its corresponding DNA methylation profiles of liver cells in normal, NAFLD&NASH, PBC&PSC, and HCC patients, we identified the genome-wide real genetic and epigenetic networks (GENs) of normal, NAFLD&NASH, PBC&PSC, and HCC patients. In order to get valuable insight into these identified genome-wide GENs, we then applied a principal network projection method to extract the corresponding core GENs for normal liver cells, NAFLD&NASH, PBC&PSC, and HCC. By comparing the signal transduction pathways involved in the identified core GENs, we found that the hepatocarcinogenesis through NAFLD&NASH was induced through DNA methylation of HIST2H2BE, HSPB1, RPL30, and ALDOB and the regulation of miR-21 and miR-122, and the hepatocarcinogenesis through PBC&PSC was induced through DNA methylation of RPL23A, HIST2H2BE, TIMP1, IGF2, RPL30, and ALDOB and the regulation of miR-29a, miR-21, and miR-122. The genetic and epigenetic changes in the pathogenesis and hepatocarcinogenesis potentially serve as potential diagnostic biomarkers and/or therapeutic targets.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Epigênese Genética , Neoplasias Hepáticas/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Metilação de DNA , Mineração de Dados , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Sequenciamento Completo do Genoma
8.
J Thorac Dis ; 10(7): 4387-4395, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30174887

RESUMO

Background: Patients with community acquired pneumonia (CAP) caused by viruses can develop severe complications, which result in hospitalization and death. The purpose of this study was to analyse the aetiology, incidence, clinical characteristics, and outcomes of CAP patients with fever during non-pandemics, and then to provide theoretical basis for accurate diagnosis and treatment in CAP patients. Methods: An enrolment system was established for monitoring the CAP patients with fever. Multiplex polymerase chain reaction (mPCR) kits were used to detect 10 viruses [influenza A and B, adenovirus (ADV), respiratory syncytial virus (RSV) A and B, picornavirus, parainfluenza virus (PIV), coronavirus, human metapneumovirus (HMPV), and bocavirus]. Data on age, gender, underlying diseases, complications, laboratory indexes, and outcomes were collected by physicians. Results: This prospective study included 320 patients with fever. Among them, 23.4% were viral-positive by mPCR, with influenza virus most prominent followed by picornavirus. Strong variation in seasonal distribution was shown in viral infections, with peak months from December to February. Patients with influenza infection were likely to be taken to emergency rooms and have respiratory failure with higher creatinine kinase levels and lower white blood cell counts. Streptococcus pneumoniae followed by haemophilus influenzae were the most common bacteria in viral co-infections, which accounted for one third of virus-positive patients. Viral CAP and mixed CAP were not independent factors for death. In addition, lactate dehydrogenase (LDH) >246 IU/L [odds ratio (OR) =7.06, 95% confidence interval (CI): 2.15-23.2, P=0.001], and serum calcium <2.18 mmol/L (OR =6.67, 95% CI: 1.42-31.3, P=0.016) were associated with death. Conclusions: Viruses play an important role in CAP patients with fever, a systematic clinical, radiological and biological analysis of these patients can contribute to effective therapy that may prevent the development of CAP and improve the outcomes. The present work showed an elaborate analysis evidence of viral infection among fever CAP inpatients.

9.
PLoS One ; 13(8): e0202537, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30133498

RESUMO

Epstein-Barr virus (EBV), also known as human herpesvirus 4, is prevalent in all human populations. EBV mainly infects human B lymphocytes and epithelial cells, and is therefore associated with their various malignancies. To unravel the cellular mechanisms during the infection, we constructed interspecies networks to investigate the molecular cross-talk mechanisms between human B cells and EBV at the first (0-24 hours) and second (8-72 hours) stages of EBV infection. We first constructed a candidate genome-wide interspecies genetic-and-epigenetic network (the candidate GIGEN) by big database mining. We then pruned false positives in the candidate GIGEN to obtain the real GIGENs at the first and second infection stages in the lytic phase by their corresponding next-generation sequencing data through dynamic interaction models, the system identification approach, and the system order detection method. The real GIGENs are very complex and comprise protein-protein interaction networks, gene/microRNA (miRNA)/long non-coding RNA regulation networks, and host-virus cross-talk networks. To understand the molecular cross-talk mechanisms underlying EBV infection, we extracted the core GIGENs including host-virus core networks and host-virus core pathways from the real GIGENs using the principal network projection method. According to the results, we found that the activities of epigenetics-associated human proteins or genes were initially inhibited by viral proteins and miRNAs, and human immune responses were then dysregulated by epigenetic modification. We suggested that EBV exploits viral proteins and miRNAs, such as EBNA1, BPLF1, BALF3, BVRF1 and miR-BART14, to develop its defensive mechanism to defeat multiple immune attacks by the human immune system, promotes virion production, and facilitates the transportation of viral particles by activating the human genes NRP1 and CLIC5. Ultimately, we propose a therapeutic intervention comprising thymoquinone, valpromide, and zebularine to act as inhibitors of EBV-associated malignancies.


Assuntos
Epigênese Genética , Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/genética , Sequenciamento de Nucleotídeos em Larga Escala , Linfócitos B/virologia , Big Data , Canais de Cloreto/genética , Mineração de Dados , Infecções por Vírus Epstein-Barr/virologia , Redes Reguladoras de Genes/genética , Herpesvirus Humano 4/patogenicidade , Interações Hospedeiro-Patógeno/genética , Humanos , MicroRNAs/genética , Proteínas dos Microfilamentos/genética , Neuropilina-1/genética , Proteínas Virais/genética
10.
Oncotarget ; 9(34): 23636-23660, 2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-29805763

RESUMO

Mutation accumulation and epigenetic alterations in genes are important for carcinogenesis. Because leukemogenesis-related signal pathways have been investigated and microarray sample data have been produced in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and normal cells, systems analysis in coupling pathways becomes possible. Based on system modeling and identification, we could construct the coupling pathways and their associated gene regulatory networks using microarray sample data. By applying system theory to the estimated system model in coupling pathways, we can then obtain transductivity sensitivity, basal sensitivity and error sensitivity of each protein to identify the potential impact of genetic mutations, epigenetic alterations and the coupling of other pathways from the perspective of energy, respectively. By comparing the results in AML, MDS and normal cells, we investigated the potential critical genetic mutations and epigenetic alterations that activate or repress specific cellular functions to promote MDS or AML leukemogenesis. We suggested that epigenetic modification of ß-catenin and signal integration of CSLs, AP-2α, STATs, c-Jun and ß-catenin could contribute to cell proliferation at AML and MDS. Epigenetic regulation of ERK and genetic mutation of p53 could lead to the repressed apoptosis, cell cycle arrest and DNA repair in leukemic cells. Genetic mutation of JAK, epigenetic regulation of ERK, and signal integration of C/EBPα could result in the promotion of MDS cell differentiation. According to the results, we proposed three drugs, decitabine, genistein, and monorden for preventing AML leukemogenesis, while three drugs, decitabine, thalidomide, and geldanamycin, for preventing MDS leukemogenesis.

11.
Clin Respir J ; 12(8): 2346-2353, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29790656

RESUMO

INTRODUCTION: Lung damage related to tuberculosis is a major contributor to the etiology of bronchiectasis in China. It is unknown whether bronchiectasis severity score systems are applicable in these cases. OBJECTIVES: To evaluate the clinical characteristics and validation of bronchiectasis severity score systems for post-tuberculosis bronchiectasis. METHODS: The study enrolled 596 bronchiectasis patients in Shanghai Pulmonary Hospital between January 2011 and December 2012. The data for calculating FACED and bronchiectasis severity index (BSI) scores along with mortality, readmission, and exacerbation outcomes were collected and analyzed within a follow-up period with a median length of 48 months (interquartile range 43-54 months). RESULTS: The study enrolled 101 post-tuberculosis bronchiectasis patients and 495 non-tuberculosis bronchiectasis patients. Compared with non-post-tuberculosis bronchiectasis, post-tuberculosis bronchiectasis patients experienced less bilateral bronchiectasis (P = .004), a higher frequency of right upper lobe involvement (P < .001) and showed the cylindrical type more often (P < .001). Follow-up data indicated that both scoring systems were able to predict 48(43-54) month mortality in post-tuberculosis patients as assessed by the area under the receiver operator characteristic curve (AUC) (FACED AUC = 0.81, BSI AUC = 0.70), but they did not predict readmission (FACED and BSI = 0.56) or exacerbation (FACED and BSI = 0.52) well. CONCLUSIONS: There are apparent differences on radiologic features between bronchiectasis patients with and without history of pulmonary tuberculosis. Both FACED and BSI can predict mortality in post-tuberculosis bronchiectasis.


Assuntos
Bronquiectasia/diagnóstico por imagem , Bronquiectasia/patologia , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/patologia , Adulto , Idoso , Bronquiectasia/mortalidade , Bronquiectasia/fisiopatologia , China/epidemiologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/mortalidade
12.
BMJ Open ; 8(3): e014613, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29540404

RESUMO

OBJECTIVES: Pseudomonas aeruginosa (P. aeruginosa) occupies an important niche in the pathogenic microbiome of bronchiectasis. The objective of this study is to evaluate the clinical characteristics and prognostic value of P. aeruginosa in Chinese adult patients with bronchiectasis. METHODS: This retrospective and follow-up study enrolled 1188 patients diagnosed with bronchiectasis at Shanghai Pulmonary Hospital between January 2011 and December 2012. The patients' clinical data including anthropometry, clinical symptoms, serum biomarkers, radiographic manifestations and lung function indices were reviewed. The median follow-up duration (IQR) was 44 (40-54) months, during which 289 patients were lost to follow-up. Data from 899 patients were collected and analysed for the outcomes of mortality, annual exacerbation frequency and health-related quality of life. RESULTS: P. aeruginosa was isolated from 232 patients, alongside other pathogens such as Aspergillus (n=75) and Candida albicans (n=72). There were 74 deaths (12% of patients with P. aeruginosa, 7.3% of those without) over the course of the follow-up. The isolation of P. aeruginosa was a risk factor for all-cause mortality (HR, 3.07; 95% CI 1.32 to 7.15) and was associated with high rates of exacerbations (ie, ≥3 exacerbations per year of follow-up) (HR, 2.40; 95% CI 1.20 to 4.79). Patients with P. aeruginosa also had worse scores on the Hospital Anxiety and Depression Scale (anxiety, p=0.005; depression, p<0.001), the Leicester Cough Questionnaire (p=0.033) and the modified Medical Research Council scale (p=0.001) compared with those without P. aeruginosa. CONCLUSIONS: Isolation of P. aeruginosa in patients with bronchiectasis is a significant prognostic indicator and should be a major factor in the clinical management of the disease.


Assuntos
Bronquiectasia/microbiologia , Infecções por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/isolamento & purificação , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Biomarcadores/análise , Bronquiectasia/mortalidade , Estudos de Casos e Controles , China/epidemiologia , Comorbidade , Depressão/diagnóstico , Depressão/epidemiologia , Progressão da Doença , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Infecções por Pseudomonas/mortalidade , Qualidade de Vida , Estudos Retrospectivos , Fatores de Tempo
13.
BMJ Open ; 8(2): e018865, 2018 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-29453299

RESUMO

OBJECTIVES: Sarcoidosis is a multisystem disease characterised by the formation of granulomas within various organs, mainly the lungs. Several studies from different countries have been undertaken to investigate sarcoidosis with extrapulmonary involvement except from China. The objective of this study is to investigate a comparative clinical analysis in patients with pulmonary sarcoidosis with and without extrapulmonary involvement from China. METHODS: Data from inpatients diagnosed with sarcoidosis at Shanghai Pulmonary Hospital (Shanghai, China) between January 2009 and December 2014 were retrospectively collected and analysed. Six hundred and thirty-six patients with biopsy-proven sarcoidosis were included in the study, including 378 isolated pulmonary sarcoidosis and 258 pulmonary sarcoidosis plus extrapulmonary involvement. RESULTS: Two hundred and fifty-eight (40.6%) patients with pulmonary sarcoidosis had extrapulmonary involvement. Extrapulmonary localisations were detected mostly in extrathoracic lymph nodes (n=147) and skin (n=86). Statistically significant differences were demonstrated between patients with pulmonary sarcoidosis plus extrapulmonary involvement and patients with isolated pulmonary sarcoidosis for fatigue (16.6%vs8.3%, P<0.05), serum ACE (SACE) levels (79.0±46.9 IU/L vs 69.7±38.7 IU/L, P<0.05), and high-resolution CT (HRCT) findings (53.8%vs46.2%, P<0.05). CONCLUSIONS: Extrapulmonary involvement is common in patients with pulmonary sarcoidosis, with the most common sites being extrathoracic lymph nodes and skin. Patients with sarcoidosis with extrapulmonary involvement are more symptomatic (fatigue), have higher SACE levels and more deteriorating HRCT findings, to which clinicians should pay attention.


Assuntos
Pulmão/patologia , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/fisiopatologia , Adulto , China , Estudos Transversais , Fadiga/epidemiologia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/sangue , Estudos Retrospectivos , Pele/patologia , Tomografia Computadorizada por Raios X
14.
Curr HIV Res ; 16(1): 77-95, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29468972

RESUMO

BACKGROUND: Two big issues in the study of pathogens are determining how pathogens infect hosts and how the host defends itself against infection. Therefore, investigating host-pathogen interactions is important for understanding pathogenicity and host defensive mechanisms and treating infections. METHODS: In this study, we used omics data, including time-course data from high-throughput sequencing, real-time polymerase chain reaction, and human microRNA (miRNA) and protein-protein interaction to construct an interspecies protein-protein and miRNA interaction (PPMI) network of human CD4+ T cells during HIV-1 infection through system modeling and identification. RESULTS: By applying a functional annotation tool to the identified PPMI network at each stage of HIV infection, we found that repressions of three miRNAs, miR-140-5p, miR-320a, and miR-941, are involved in the development of autoimmune disorders, tumor proliferation, and the pathogenesis of T cells at the reverse transcription stage. Repressions of miR-331-3p and miR-320a are involved in HIV-1 replication, replicative spread, anti-apoptosis, cell proliferation, and dysregulation of cell cycle control at the integration/replication stage. Repression of miR-341-5p is involved in carcinogenesis at the late stage of HIV-1 infection. CONCLUSION: By investigating the common core proteins and changes in specific proteins in the PPMI network between the stages of HIV-1 infection, we obtained pathogenic insights into the functional core modules and identified potential drug combinations for treating patients with HIV-1 infection, including thalidomide, oxaprozin, and metformin, at the reverse transcription stage; quercetin, nifedipine, and fenbendazole, at the integration/replication stage; and staurosporine, quercetin, prednisolone, and flufenamic acid, at the late stage.


Assuntos
Infecções por HIV/virologia , HIV-1/fisiologia , Interações Hospedeiro-Patógeno , Algoritmos , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Biologia Computacional , Mineração de Dados , Descoberta de Drogas/métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , HIV-1/efeitos dos fármacos , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Modelos Teóricos , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Biologia de Sistemas/métodos
15.
Front Immunol ; 8: 901, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28824629

RESUMO

Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea and the major etiologic agent of pseudomembranous colitis. In severe cases, C. difficile infection (CDI) can cause toxic megacolon, intestinal perforation, and death. The intestinal epithelium is the first tissue encountered in the adhesion and colonization of C. difficile, and serves as a physical defense barrier against infection. Despite the well-characterized cytotoxicity, few studies have investigated the genome-wide interplay between host cells and C. difficile. The aim of this study is to investigate the genetic-and-epigenetic molecular mechanisms between human colorectal epithelial Caco-2 cells and C. difficile during the early (0-60 min) and late stages (30-120 min) of infection. To investigate the cross-talk mechanisms during the progression of infection, we introduced a systems biology approach using big data mining, dynamic network modeling, a genome-wide data identification method, system order detection scheme, and principal network projection method (PNP). We focused on the construction of genome-wide genetic-and-epigenetic interspecies networks (GEINs) and subsequent extraction of host-pathogen core networks (HPNs) to investigate the progression of underlying host/pathogen genetic-and-epigenetic mechanisms from the early to late stages of CDI. Based on our results, we suggest that the cell-wall proteins CD2787 and CD0237, which both play an important role in cell adhesion and pathogen defense mechanisms, can be considered as potential drug targets. In addition, the crucial proteins employed by C. difficile for sporulation, including CD1214, CD2629, and CD2643, can also be considered as potential drug targets since spore-mediated re-infection is a critical issue.

16.
J Thorac Dis ; 9(2): 247-253, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28275471

RESUMO

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a fungal infection frequently observed in patients with immune dysfunction, such as those suffering from structural lung diseases. Nevertheless, studies assessing IPA combined with other common respiratory diseases remain scarce, particularly those regarding the immune status of its patients. Different structural lung diseases are known to differently affect patient immune status; however, the mechanisms by which this is conferred have yet to be determined. Thus, our study aims to compare the immune status of IPA patients with the structural lung diseases chronic obstructive pulmonary diseases (COPD), interstitial lung disease (ILD) and non-cystic fibrosis bronchiectasis (NCFB). METHODS: This study was performed retrospectively with data collected over the years 2004 to 2013 at Shanghai Pulmonary Hospital, Tongji University, and included 77 patients whose lower respiratory tract (LRT) samples tested positive for. Our analysis considered blood examinations of CD3+, CD4+, CD8+, CD4+/CD8+, IgG, IgA and IgM levels. RESULTS: CD4+/CD8+ double positive cells, representing cell-mediated immunity, were less abundant in IPA patients with COPD than those with ILD and NCFB (0.81±0.09 vs. 1.39±0.25 and 0.81±0.09 vs. 1.57±0.06, respectively, P<0.001). In agreement with this result, corticosteroid and broad-spectrum antibiotic use were most common in individuals with COPD (57%). IgA levels, which indicate humoral immunity, were lower in IPA patients with NCFB than those with COPD or ILD (0.95±0.28 vs. 1.64±0.40 g/L and 0.95±0.28 vs. 3.16±0.83 g/L, respectively, P<0.001). CONCLUSIONS: Immunity status differs between IPA patients with different structural lung diseases. Among IPA patients with COPD, ILD and NCFB, those with COPD have the lowest cell-mediated immunity, while those with NCFB have the lowest humoral immunity.

17.
Ying Yong Sheng Tai Xue Bao ; 28(7): 2307-2314, 2017 Jul 18.
Artigo em Chinês | MEDLINE | ID: mdl-29741064

RESUMO

Pb stable isotope signatures analysis can be used to identify its sources precisely and the spatial transportation process to achieve precise management of target areas. In this study, 12 surface (0-10 cm) soil samples (3-5 replications for each site) were collected on the Yancheng coast. Pb isotopes (206Pb, 207Pb and 208Pb) and Pb contents were analyzed by inductively coupled plasma mass spectrometry. Results showed that the soil Pb contents were as high as 1.7 times of the background Pb content value. Referencing the national criteria of GB 15618-2008, the study area was polluted by Pb to a relatively serious extent. The analysis indicated that main Pb sources of the area were local, including Sheyang Power Plant, Shuangdeng Paper Mill Sewage Plant, and Huafeng industrial area near Wanggang. Based on the normalized difference vegetation index (NDVI) and distance analysis, we figured out the key patterns of Yancheng coast to cope with the press sources.


Assuntos
Monitoramento Ambiental , Chumbo , Isótopos , Solo , Poluentes do Solo
18.
Artigo em Inglês | MEDLINE | ID: mdl-27803888

RESUMO

Tuberculosis is caused by Mycobacterium tuberculosis (Mtb) infection. Mtb is one of the oldest human pathogens, and evolves mechanisms implied in human evolution. The lungs are the first organ exposed to aerosol-transmitted Mtb during gaseous exchange. Therefore, the guards of the immune system in the lungs, such as macrophages (Mϕs) and dendritic cells (DCs), are the most important defense against Mtb infection. There have been several studies discussing the functions of Mϕs and DCs during Mtb infection, but the genome-wide pathways and networks are still incomplete. Furthermore, the immune response induced by Mϕs and DCs varies. Therefore, we analyzed the cross-talk genome-wide genetic-and-epigenetic interspecies networks (GWGEINs) between Mϕs vs. Mtb and DCs vs. Mtb to determine the varying mechanisms of both the host and pathogen as it relates to Mϕs and DCs during early Mtb infection. First, we performed database mining to construct candidate cross-talk GWGEIN between human cells and Mtb. Then we constructed dynamic models to characterize the molecular mechanisms, including intraspecies gene/microRNA (miRNA) regulation networks (GRNs), intraspecies protein-protein interaction networks (PPINs), and the interspecies PPIN of the cross-talk GWGEIN. We applied a system identification method and a system order detection scheme to dynamic models to identify the real cross-talk GWGEINs using the microarray data of Mϕs, DCs and Mtb. After identifying the real cross-talk GWGEINs, the principal network projection (PNP) method was employed to construct host-pathogen core networks (HPCNs) between Mϕs vs. Mtb and DCs vs. Mtb during infection process. Thus, we investigated the underlying cross-talk mechanisms between the host and the pathogen to determine how the pathogen counteracts host defense mechanisms in Mϕs and DCs during Mtb H37Rv early infection. Based on our findings, we propose Rv1675c as a potential drug target because of its important defensive role in Mϕs. Furthermore, the membrane essential proteins v1098c, and Rv1696 (or cytoplasm for Rv0667), in Mtb could also be potential drug targets because of their important roles in Mtb survival in both cell types. We also propose the drugs Lopinavir, TMC207, ATSM, and GTSM as potential therapeutic treatments for Mtb infection since they target the above potential drug targets.


Assuntos
Células Dendríticas/imunologia , Epigênese Genética , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno , Macrófagos/imunologia , Mycobacterium tuberculosis/patogenicidade , Tuberculose/imunologia , Biologia Computacional , Humanos , Evasão da Resposta Imune , Análise em Microsséries
19.
Oncotarget ; 7(48): 79453-79473, 2016 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-27821810

RESUMO

The mechanisms leading to the development and progression of hepatocellular carcinoma (HCC) are complicated and regulated genetically and epigenetically. The recent advancement in high-throughput sequencing has facilitated investigations into the role of genetic and epigenetic regulations in hepatocarcinogenesis. Therefore, we used systems biology and big database mining to construct genetic and epigenetic networks (GENs) using the information about mRNA, miRNA, and methylation profiles of HCC patients. Our approach involves analyzing gene regulatory networks (GRNs), protein-protein networks (PPINs), and epigenetic networks at different stages of hepatocarcinogenesis. The core GENs, influencing each stage of HCC, were extracted via principal network projection (PNP). The pathways during different stages of HCC were compared. We observed that extracellular signals were further transduced to transcription factors (TFs), resulting in the aberrant regulation of their target genes, in turn inducing mechanisms that are responsible for HCC progression, including cell proliferation, anti-apoptosis, aberrant cell cycle, cell survival, and metastasis. We also selected potential multiple drugs specific to prominent epigenetic network markers of each stage of HCC: lestaurtinib, dinaciclib, and perifosine against the NTRK2, MYC, and AKT1 markers influencing HCC progression from stage I to stage II; celecoxib, axitinib, and vinblastine against the DDIT3, PDGFB, and JUN markers influencing HCC progression from stage II to stage III; and atiprimod, celastrol, and bortezomib against STAT3, IL1B, and NFKB1 markers influencing HCC progression from stage III to stage IV.


Assuntos
Carcinoma Hepatocelular/genética , Biologia Computacional/métodos , Epigênese Genética , Redes Reguladoras de Genes , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/patologia , Metilação de DNA , Mineração de Dados , Progressão da Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Estadiamento de Neoplasias , Análise de Sequência de DNA , Biologia de Sistemas
20.
J Thorac Dis ; 8(6): 1283-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27293848

RESUMO

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is an orphan disease in respiratory medicine, which most affects adult smokers. The purpose of this article was to discuss the clinical features, especially the radiologic features of PLCH patients during their hospitalization through a retrospective analysis on clinical data. Furthermore, the current literature was also reviewed. METHODS: Between December 2008 and June 2012, 14 patients with PLCH were assessed at Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Among these patients, seven patients were diagnosed through tissue biopsy from the lung and one patient from enlarged cervical lymph nodes; the rest of six patients were diagnosed based on the clinical-radiological data. The data consisting of demographics, clinical presentation, smoking habits, pulmonary function tests (PFTs) and radiographic image from the medical records was analyzed retrospectively. RESULTS: The average age of patients (11 males and 3 females) was 42.79 (±13.71) years old. All male patients and one female patient had a long smoking history. The common manifestations were cough and exertional dyspnea. Spontaneous pneumothorax was found in three patients. Varieties of pulmonary shadows such as nodular, cystic, patch-like and cord-like were revealed by chest computed tomography (CT) examination. Large Langerhans cells (LCs) were discovered in biopsy tissue by immunohistochemical stains. CONCLUSIONS: PLCH is still an orphan disease and maybe related to smoking. Clinical symptoms such as cough and exertional dyspnea are non-specific. We shall pay attention to recurrent pneumothorax as clinically it is associated with PLCH. The characteristic radiological manifestation is cystic or nodular shadow in the lungs, which plays crucial roles in diagnosing PLCH.

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