scholarly journals Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in COPD

2019 ◽  
Vol 53 (4) ◽  
pp. 1801202 ◽  
Author(s):  
Alen Faiz ◽  
Katrina Steiling ◽  
Mirjam P. Roffel ◽  
Dirkje S. Postma ◽  
Avrum Spira ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Corticosteroid Treatment ◽  
Nuclear Factor Κb ◽  
Airway Epithelial Cells ◽  
Chronic Obstructive ◽  
Functional Studies ◽  
Copd Patients ◽  
Epithelial Cultures

The aim was to investigate whether microRNA (miRNA) expression is modulated by inhaled corticosteroid (ICS) treatmentWe performed genome-wide miRNA analysis on bronchial biopsies of 69 moderate/severe chronic obstructive pulmonary disease (COPD) patients at baseline and after 6- and 30-month treatment with the ICS fluticasone propionate or placebo. The effect of ICS on miRNA expression was validated in differentiated primary bronchial epithelial cultures, and functional studies were conducted in BEAS-2B cells. MiRNAs affected by ICS and their predicted targets were compared to an independent miRNA dataset of bronchial brushings from COPD patients and healthy controls.Treatment with ICS for both 6 and 30 months significantly altered the expression of four miRNAs, including miR-320d, which was increased during ICS treatment compared with placebo. The ICS-induced increase of miR-320d was confirmed in primary airway epithelial cells. MiR-320d negatively correlated targets were enriched for pro-inflammatory genes and were increased in the bronchial brushes of patients with lower lung function in the independent dataset. Overexpression of miR-320d in BEAS-2B cells dampened cigarette smoke extract-induced pro-inflammatory activity via inhibition of nuclear factor-κB.Collectively, we identified miR-320d as a novel mediator of ICS, regulating the pro-inflammatory response of the airway epithelium.

scholarly journals Dynamics and Innovations within Oomycete Genomes: Insights into Biology, Pathology, and Evolution

2012 ◽  
Vol 11 (11) ◽  
pp. 1304-1312 ◽  
Author(s):  
Howard S. Judelson
Keyword(s):  
Protein Sequence ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Life Cycles ◽  
Aquatic Environments ◽  
Gene Fusions ◽  
Additional Species ◽  
Functional Studies ◽  
Eukaryotic Microbes ◽  
Genome Projects

ABSTRACT The eukaryotic microbes known as oomycetes are common inhabitants of terrestrial and aquatic environments and include saprophytes and pathogens. Lifestyles of the pathogens extend from biotrophy to necrotrophy, obligate to facultative pathogenesis, and narrow to broad host ranges on plants or animals. Sequencing of several pathogens has revealed striking variation in genome size and content, a plastic set of genes related to pathogenesis, and adaptations associated with obligate biotrophy. Features of genome evolution include repeat-driven expansions, deletions, gene fusions, and horizontal gene transfer in a landscape organized into gene-dense and gene-sparse sectors and influenced by transposable elements. Gene expression profiles are also highly dynamic throughout oomycete life cycles, with transcriptional polymorphisms as well as differences in protein sequence contributing to variation. The genome projects have set the foundation for functional studies and should spur the sequencing of additional species, including more diverse pathogens and nonpathogens.

scholarly journals The systemic nature of mustard lung: Comparison with COPD patients

2017 ◽  
Vol 10 (3) ◽  
pp. 114-127 ◽  
Author(s):  
Alireza Shahriary ◽  
Mostafa Ghanei ◽  
Hossein Rahmani
Keyword(s):  
Clinical Symptoms ◽  
Airway Remodeling ◽  
Serum Levels ◽  
Nuclear Factor Κb ◽  
Chemical Warfare Agent ◽  
Pulmonary Complications ◽  
Chronic Obstructive ◽  
Necrosis Factor Alpha ◽  
Copd Patients ◽  
Systemic Nature

AbstractSulphur mustard (SM) is a powerful blister-causing alkylating chemical warfare agent used by Iraqi forces against Iran. One of the known complications of mustard gas inhalation is mustard lung which is discussed as a phenotype of chronic obstructive pulmonary disease (COPD). In this complication, there are clinical symptoms close to COPD with common etiologies, such as in smokers. Based on information gradually obtained by conducting the studies on mustard lung patients, systemic symptoms along with pulmonary disorders have attracted the attention of researchers. Changes in serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), nuclear factor κB (NF-κB), matrix metalloproteinases (MMPs), interleukin (IL), chemokines, selectins, immunoglobulins, and signs of imbalance in oxidant-antioxidant system at serum level, present the systemic changes in these patients. In addition to these, reports of extra-pulmonary complications, such as osteoporosis and cardiovascular disease are also presented. In this study, the chance of developing the systemic nature of this lung disease have been followed on using the comparative study of changes in the mentioned markers in mustard lung and COPD patients at stable phases and the mechanisms of pathogenesis and phenomena, such as airway remodeling in these patients.

scholarly journals Proteasome Inhibitors Interrupt the Activation of Non-Canonical NF-κB Signaling Pathway and Induce Cell Apoptosis in Cytarabine-Resistant HL60 Cells

2021 ◽  
Vol 23 (1) ◽  
pp. 361
Author(s):  
Shuo-Yu Wang ◽  
Yin-Hwa Shih ◽  
Tzong-Ming Shieh ◽  
Yu-Hsin Tseng
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Expression Profiles ◽  
Proteasome Inhibitors ◽  
Gene Expression Profiles ◽  
Nuclear Factor Κb ◽  
High Dose ◽  
Hl60 Cells ◽  
Expression Arrays ◽  
Study Results

Over half of older patients with acute myeloid leukemia (AML) do not respond to cytotoxic chemotherapy, and most responders relapse because of drug resistance. Cytarabine is the main drug used for the treatment of AML. Intensive treatment with high-dose cytarabine can increase the overall survival rate and reduce the relapse rate, but it also increases the likelihood of drug-related side effects. To optimize cytarabine treatment, understanding the mechanism underlying cytarabine resistance in leukemia is necessary. In this study, the gene expression profiles of parental HL60 cells and cytarabine-resistant HL60 (R-HL60) cells were compared through gene expression arrays. Then, the differential gene expression between parental HL60 and R-HL60 cells was measured using KEGG software. The expression of numerous genes associated with the nuclear factor κB (NF-κB) signaling pathway changed during the development of cytarabine resistance. Proteasome inhibitors inhibited the activity of non-canonical NF-κB signaling pathway and induced the apoptosis of R-HL60 cells. The study results support the application and possible mechanism of proteasome inhibitors in patients with relapsed or refractory leukemia.

scholarly journals De novo characterization of the Lycium ruthenicum transcriptome and analysis of its digital gene expression profiles during fruit development and ripening

2017 ◽  
Vol 69 (1) ◽  
pp. 181-190 ◽  
Author(s):  
Yong Peng ◽  
Huiqin Ma ◽  
Shangwu Chen
Keyword(s):  
Gene Expression ◽  
Developmental Stages ◽  
De Novo ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Digital Gene Expression ◽  
Orthologous Group ◽  
Functional Studies ◽  
Lycium Ruthenicum

Lycium ruthenicum Murr., which belongs to the family Solanaceae, is a resource plant for Chinese traditional medicine and nutraceutical foods. In this study, RNA sequencing was applied to obtain raw reads of L. ruthenicum fruit at different stages of ripening, and a de novo assembly of its sequence was performed. Approximately 52.45 million 100-bp paired-end raw reads were generated from the samples by deep RNA-seq analysis. These short reads were assembled to obtain 164814 contigs, and the contigs were assembled into 84968 non-redundant unigenes using the Trinity method. Assembled sequences were annotated with gene descriptions, gene ontology, clusters of orthologous group and KEGG (Kyoto Encyclopedia of Genes and Genomes)pathway terms. Digital gene expression analysis was applied to compare gene-expression patterns at different fruit developmental stages. These results contribute to existing sequence resources for Lycium spp. during the fruit-ripening stages, which is valuable for further functional studies of genes involved in L. ruthenicum fruit nutraceutical quality.

scholarly journals CircRNA Expression Profile in Lung Cancer Complicated with Chronic Obstructive Pulmonary Disease Patients

2020 ◽  
Author(s):  
Fuqiang Wen ◽  
Xiaoou Li ◽  
Yongchun Shen ◽  
Jiahan Cheng ◽  
Jun Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Expression Profiles ◽  
Circular Rnas ◽  
Chronic Obstructive ◽  
Biological Processes ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Diagnosis Of Lung Cancer

Abstract Background: Lung cancer complicated with chronic obstructive pulmonary disease (COPD) are major causes of mortality worldwide, and the incidence of lung cancer and COPD increasing significantly. Circular RNAs (circRNAs), have been reported to participate in various biological processes, whereas the role of circRNAs in lung cancer complicated with COPD remains unclear. We aims to identify differentially expressed circRNAs (DEcircRNAs) between lung cancer complicated with COPD and lung cancer without COPD. Method: The circRNAs expression profiles were identified using a high-throughput circRNA microarray in cancer adjacent tissues from 6 lung cancer without COPD patients and 8 lung cancer complicated with COPD patients. Bioinformatic analyses were conducted to identify the functions of DEcircRNAs. Result: A total of 115 up- and 128 down-regulated circRNAs were screened in lung cancer complicated with COPD patients compared with lung cancer without COPD patients. The myD88-dependent toll-like receptor signaling pathway and positive regulation of nitric oxide biosynthetic process ranked the top 2 enriched biological processes in Gene Ontology analysis. Signaling transduction and infectious diseases were the most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways in both up- and down-regulated circRNAs. Compared with lung cancer without COPD, circRNAs are dysregulated in the adjacent tissues of lung cancer with COPD. Conclusion: The DEcircRNAs might act as potential targets for the diagnosis of lung cancer with COPD.

A comprehensive view of the structure and expression of the ependymoma genome at presentation and relapse

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2073-2073
Author(s):  
K. D. Wright ◽  
V. Rand ◽  
S. E. Leary ◽  
S. Mack ◽  
B. Coyle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genetic Alterations ◽  
Specific Gene ◽  
Mortality And Morbidity ◽  
Distinct Subgroup ◽  
Comprehensive View ◽  
Genomic Study

2073 Background: Although pediatric and adult ependymomas are associated with significant mortality and morbidity, little is known about the biology of these tumors. To identify underlying genetic alterations and cellular pathways that drive this disease, we conducted a genomic study of 200 adult and pediatric ependymomas. Methods: Using 500k single nucleotide polymorphism arrays, U133 Affymetrix gene and microRNA (miRNA) expression microarrays, and appropriate bioinformatics, we characterized 56 supratentorial (ST), 104 posterior fossa (PF), and 40 spinal (SP) ependymomas. Real-Time polymerase chain reaction and fluorescence in situ hybridization validated observed genetic events. Results: Gene expression profiles segregated tumors by site and identified disease subgroups within each anatomical region (4 ST, 4 PF, 1 SP). miRNA expression profiles identified these same subgroups, indicating that they are biologically distinct. Subgroup-specific gene expression profiles were dictated partly by developmental regulatory genes and partly by large chromosomal gains (eg. 1q, 5p, 16p) and losses (eg. 9p, 22q). Integrated genetic and expression mapping revealed key candidate tumor suppressor (TSG) and onco- genes, likely drivers of these large alterations. While large chromosomal changes occurred more frequently in SP tumors (p < 0.0001), ST tumors averaged more focal changes (n = 13.2) than PF (n = 6.2) or SP tumors (n = 3.0) (p < 0.0001). A total of 29 and 33 non-random focal amplifications and deletions, respectively, encompassing 402 known genes and miRNA clusters, were validated, of which 80 displayed copy number driven expression. These genetic alterations targeted specific cellular functions (e.g., cell adhesion, cell-cycle, neuronal development) and pathways (e.g., NOTCH, EPHRIN, TP53). Our cohort also included five sample sets consisting of primary tumor and at least two corresponding relapses. Genomic analysis of these tumors identified large chromosomal alterations as well as focal gains and losses associated with disease relapse. Conclusions: We present a highly comprehensive view of the ependymoma genome, including 80 previously unrecognized candidate TSG and oncogenes that may afford diagnostic and therapeutic targets. No significant financial relationships to disclose.

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