Evidence of altered brain regulatory gene expression in tobacco-exposed fetuses

AbstractAim:We sought to determine the association between prenatal smoking status and expression of fetal brain regulatory genes.Methods:At delivery, we collected information from parturient women on prenatal smoking habits and analyzed salivary cotinine levels. We obtained neonatal umbilical cord blood and extracted total RNA. We then employed the quantitative polymerase chain reaction (QPCR) analyses and the comparative CT method to calculate the relative gene expression of selected fetal brain regulatory genes responsible for (1) brain growth (brain-derived neutrotrophic factor, BDNF), (2) myelination (proteolipidic protein 1, PLP1 and myelin basic protein, MBP), and (3) neuronal migration and cell-cell interactions during fetal brain development or RLN. The χResults:Of the 39 maternal-infant dyads included in this study, 25.6% were non-smokers, 43.6% were passive smokers and 30.8% were active smokers. The results showed down-regulation of the selected fetal brain regulatory genes among active smokers.Conclusions:These findings represent preliminary evidence in humans that intrauterine tobacco exposure impacts fetal brain programming. Future studies are warranted to examine whether our findings represent potential mechanisms through which adverse childhood/adult-onset cognitive and behavioral outcomes that have been previously linked to intrauterine exposure occur.

Download Full-text

Evaluation of Selected IL6/STAT3 Pathway Molecules and miRNA Expression in Chronic Obstructive Pulmonary Disease - the Search for New Diagnostic Markers

10.21203/rs.3.rs-270593/v1 ◽

2021 ◽

Author(s):

Justyna Kiszałkiewicz ◽

Sebastian Majewski ◽

Wojciech J. Piotrowski ◽

Paweł Górski ◽

Dorota Pastuszak-Lewandoska ◽

...

Keyword(s):

Gene Expression ◽

Mirna Expression ◽

Smoking Status ◽

Control Group ◽

Chronic Obstructive ◽

Tobacco Exposure ◽

Expression Levels ◽

Stat3 Pathway ◽

Global Epidemic ◽

Gene Expression Levels

Abstract Background COPD has been regarded as a global epidemic due to an increase in pollution and tobacco exposure. Therefore, the study of molecular mechanism as the basis for modern therapy is important. Objective The aim of the study was the assessment of gene expression levels, IL-6, IL-6ST, PIAS3, STAT3, and miRNAs, miR-1, miR-106b, miR-155, in patients with COPD. Methods Induced sputum as well as PBMC were collected from 40 patients clinically verified according to the GOLD 2017 (A-D) classification and from the control group (n = 20). The levels of gene and miRNA expression were analysed by qPCR. Results Statistically significant differences between the study group vs. control group were observed for IL-6 (P = 0.008, Mann-Whitney U test), and miR-155 (P = 0.03, Mann-Whitney U test). There were statistically significant differences between patients: current smokers vs. ex- smokers for STAT3, (P = 0.04, Mann-Whitney U test) and miR-155 (P = 0.03, Mann-Whitney U test) with a higher expression in current smokers. Conclusions Differences in gene expression levels of the IL-6 / gp130 / STAT3 pathway and miRNA depending on the smoking status and classification of patients according to GOLD suggest the importance of these genes in the pathogenesis of COPD and may indicate their potential utility in monitoring the course of the disease.

Download Full-text

Elevated plasma level of Pentraxin 3 is associated with emphysema and mortality in smokers

Thorax ◽

10.1136/thoraxjnl-2020-215356 ◽

2021 ◽

pp. thoraxjnl-2020-215356

Author(s):

Yingze Zhang ◽

John Tedrow ◽

Mehdi Nouraie ◽

Xiaoyun Li ◽

Divay Chandra ◽

...

Keyword(s):

Gene Expression ◽

Hyaluronic Acid ◽

Lung Tissue ◽

Regulatory Gene ◽

Airflow Obstruction ◽

Chronic Obstructive ◽

Pentraxin 3 ◽

Tobacco Exposure ◽

Regulatory Variants ◽

Emphysema Severity

BackgroundPentraxin 3 (PTX3) influences innate immunity and inflammation, host defence, the complement cascade and angiogenesis. PTX3 expression in lung and blood of subjects with tobacco exposure, and its potential relationship with disease pattern and clinical outcome are poorly understood.MethodsUsing independent platforms and cohorts, we identified associations of PTX3 gene expression in lung tissue and plasma from current and former tobacco smokers (with and without chronic obstructive pulmonary disease, COPD) to disease phenotypes including quantitative CT determined emphysema, lung function, symptoms and survival. Two putative regulatory variants of the PTX3 gene were examined for association with COPD manifestations. The relationship between plasma PTX3 and hyaluronic acid levels was further examined.ResultsPTX3 gene expression in lung tissue was directly correlated with emphysema severity (p<0.0001). Circulating levels of PTX3 were inversely correlated with FEV1 (p=0.006), and positively associated with emphysema severity (p=0.004) and mortality (p=0.008). Two PTX3 gene regulatory variants were associated with a lower risk for emphysema and expiratory airflow obstruction, and plasma levels of PTX3 and hyaluronic acid were related.ConclusionsThese data show strong and overlapping associations of lung and blood PTX3 levels, and PTX3 regulatory gene variants, with the severity of airflow obstruction, emphysema and mortality among smokers. These findings have potential implications regarding the pathogenesis of smoking-related lung diseases and warrant further exploration for the use of PTX3 as a predictive biomarker.

Download Full-text

PvrA is a novel regulator that contributes to Pseudomonas aeruginosa pathogenesis by controlling bacterial utilization of long chain fatty acids

Nucleic Acids Research ◽

10.1093/nar/gkaa377 ◽

2020 ◽

Vol 48 (11) ◽

pp. 5967-5985

Author(s):

Xiaolei Pan ◽

Zheng Fan ◽

Lei Chen ◽

Chang Liu ◽

Fang Bai ◽

...

Keyword(s):

Gene Expression ◽

Pseudomonas Aeruginosa ◽

Fatty Acid ◽

Coenzyme A ◽

Regulatory Gene ◽

Global Gene Expression ◽

Bacterial Virulence ◽

Regulatory Genes ◽

Bacterial Utilization ◽

Target Promoters

Abstract During infection of a host, Pseudomonas aeruginosa orchestrates global gene expression to adapt to the host environment and counter the immune attacks. P. aeruginosa harbours hundreds of regulatory genes that play essential roles in controlling gene expression. However, their contributions to the bacterial pathogenesis remain largely unknown. In this study, we analysed the transcriptomic profile of P. aeruginosa cells isolated from lungs of infected mice and examined the roles of upregulated regulatory genes in bacterial virulence. Mutation of a novel regulatory gene pvrA (PA2957) attenuated the bacterial virulence in an acute pneumonia model. Chromatin immunoprecipitation (ChIP)-Seq and genetic analyses revealed that PvrA directly regulates genes involved in phosphatidylcholine utilization and fatty acid catabolism. Mutation of the pvrA resulted in defective bacterial growth when phosphatidylcholine or palmitic acid was used as the sole carbon source. We further demonstrated that palmitoyl coenzyme A is a ligand for the PvrA, enhancing the binding affinity of PvrA to its target promoters. An arginine residue at position 136 was found to be essential for PvrA to bind palmitoyl coenzyme A. Overall, our results revealed a novel regulatory pathway that controls genes involved in phosphatidylcholine and fatty acid utilization and contributes to the bacterial virulence.

Download Full-text

Abstract 18874: A microRNA Signature of Tobacco Exposure

Circulation ◽

10.1161/circ.130.suppl_2.18874 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Christine Willinger ◽

Jian Rong ◽

Tianxiao Huan ◽

Kahraman Tanriverdi ◽

Paul Courchesne ◽

...

Keyword(s):

Gene Expression ◽

Expression Profiling ◽

Intracellular Transport ◽

Linear Models ◽

Smoking Status ◽

Study Participant ◽

Enrichment Analysis ◽

Mirna Signature ◽

Tobacco Exposure

BACKGROUND: Smoking is a cardinal risk factor for cardiovascular disease, and microRNAs (miRNAs) are key regulators of gene expression that may be involved in the development of smoking-related diseases. We sought to unravel the relationship between miRNAs and smoking by describing a miRNA signature of tobacco exposure and relating these results to the expression of smoking-associated genes. METHODS: Expression profiling of 333 miRNAs was conducted on whole blood RNA from 5,728 Framingham Heart Study participant samples using TaqMan assays and high-throughput qRT-PCR. Smoking status was classified as current, former, or never. The association of miRNA expression with smoking status was tested using general linear models, and significant miRNAs were analyzed in pairwise comparisons. Smoking-related mRNA expression associations were identified from gene expression profiling of the same RNA samples with the Affymetrix Human Exon Array ST v1.0. MiRNA-mRNA coexpression was analyzed using linear mixed effects models. RESULTS: Seven miRNAs were associated with smoking status: miR-1180, miR-181a2-3p, miR-423-5p, miR-25-5p, miR-1285-3p, miR-342-5p, and miR-744-3p (Table 1). 1,626 gene transcripts were coexpressed with one or more smoking-related miRNAs. Gene ontology enrichment analysis implicated the coexpressed genes in multiple biological processes, e.g., the ubiquitin cycle, intracellular transport, and DNA metabolism. Four genes were coexpressed with all seven smoking-associated miRNAs; most notable were TMEM56 , reported to be associated with coronary heart disease, and DOCK8 , which has been linked to lung cancer in vitro . CONCLUSIONS: We identified a novel miRNA signature of tobacco exposure featuring decreased expression of miRNAs in smokers. Our coexpression results implicate these miRNAs in smoking-related diseases and suggest broad regulatory effects on protein synthesis and turnover. TABLE 1. miRNA Associations with Smoking Status

Download Full-text

Modulation of the Tissue Expression Pattern of Zebrafish CRP-Like Molecules Suggests a Relevant Antiviral Role in Fish Skin

Biology ◽

10.3390/biology10020078 ◽

2021 ◽

Vol 10 (2) ◽

pp. 78

Author(s):

Melissa Bello-Perez ◽

Mikolaj Adamek ◽

Julio Coll ◽

Antonio Figueras ◽

Beatriz Novoa ◽

...

Keyword(s):

Gene Expression ◽

Bacterial Infections ◽

Quantitative Polymerase Chain Reaction ◽

Tissue Expression ◽

Interferon Response ◽

Fish Skin ◽

Tissue Expression Pattern ◽

Chain Reaction ◽

Polymerase Chain ◽

Antiviral Role

Recent studies suggest that short pentraxins in fish might serve as biomarkers for not only bacterial infections, as in higher vertebrates including humans, but also for viral ones. These fish orthologs of mammalian short pentraxins are currently attracting interest because of their newly discovered antiviral activity. In the present work, the modulation of the gene expression of all zebrafish short pentraxins (CRP-like proteins, CRP1-7) was extensively analyzed by quantitative polymerase chain reaction. Initially, the tissue distribution of crp1-7 transcripts and how the transcripts varied in response to a bath infection with the spring viremia of carp virus, were determined. The expression of crp1-7 was widely distributed and generally increased after infection (mostly at 5 days post infection), except for crp1 (downregulated). Interestingly, several crp transcription levels significantly increased in skin. Further assays in mutant zebrafish of recombinant activation gene 1 (rag1) showed that all crps (except for crp2, downregulated) were already constitutively highly expressed in skin from rag1 knockouts and only increased moderately after viral infection. Similar results were obtained for most mx isoforms (a reporter gene of the interferon response), suggesting a general overcompensation of the innate immunity in the absence of the adaptive one.

Download Full-text

A First Step towards Learning which uORFs Regulate Gene Expression

Journal of Integrative Bioinformatics ◽

10.1515/jib-2006-31 ◽

2006 ◽

Vol 3 (2) ◽

pp. 109-122 ◽

Cited By ~ 1

Author(s):

◽

Christopher H. Bryant ◽

Graham J.L. Kemp ◽

Marija Cvijovic

Keyword(s):

Gene Expression ◽

Inductive Logic ◽

Preliminary Evidence ◽

Open Reading Frames ◽

Yeast Saccharomyces Cerevisiae ◽

Regulate Gene Expression ◽

Integrative System ◽

Upstream Open Reading Frames ◽

Reading Frames ◽

Regulate Gene

Summary We have taken a first step towards learning which upstream Open Reading Frames (uORFs) regulate gene expression (i.e., which uORFs are functional) in the yeast Saccharomyces cerevisiae. We do this by integrating data from several resources and combining a bioinformatics tool, ORF Finder, with a machine learning technique, inductive logic programming (ILP). Here, we report the challenge of using ILP as part of this integrative system, in order to automatically generate a model that identifies functional uORFs. Our method makes searching for novel functional uORFs more efficient than random sampling. An attempt has been made to predict novel functional uORFs using our method. Some preliminary evidence that our model may be biologically meaningful is presented.

Download Full-text

Smoking status and second-hand smoke biomarkers in COPD, asthma and healthy controls

ERJ Open Research ◽

10.1183/23120541.00192-2019 ◽

2020 ◽

Vol 6 (2) ◽

pp. 00192-2019 ◽

Cited By ~ 1

Author(s):

Matteo Bradicich ◽

Macé M. Schuurmans

Keyword(s):

Sensitivity And Specificity ◽

Smoking Status ◽

Final Analysis ◽

Integrated Approach ◽

Second Hand Smoke ◽

Healthy Controls ◽

Tobacco Exposure ◽

Urinary Cotinine ◽

Pubmed Database ◽

Shs Exposure

IntroductionTobacco smoke worsens COPD and asthma. For healthy individuals, quantifying active and second-hand smoke (SHS) exposure clarifies the epidemiology of tobacco consumption and the efficacy of nonsmoking measures. Identifying tobacco exposure biomarkers and cut-offs might allow the creation of sensitive and specific tests.AimWe describe the state-of-the-art serum, urinary cotinine and exhaled carbon monoxide (CO) cut-offs for assessing smoking status and SHS exposure in adult patients with COPD or asthma, and healthy controls.MethodologyAfter a keyword research in the PubMed database, we included papers reporting on the cut-offs of the investigated biomarkers in one of the populations of interest. Papers published before 2000, not in English, or reporting only data on nonadult subjects or on pregnant women were excluded from the analysis. 14 papers were included in the final analysis. We summarised diagnostic cut-offs for smoking status or SHS exposure in COPD, asthmatic and healthy control cohorts, reporting sensitivity and specificity when available.ConclusionSerum and urinary cotinine and exhaled CO are easy-to-standardise, affordable and objective tests for assessing smoking status and SHS exposure. Evidence on cut-offs with good sensitivity and specificity values is available mainly for healthy controls. For COPD and asthmatic patients, most of the currently available evidence focuses on exhaled CO, while studies on the use of cotinine with definite sensitivity and specificity values are still missing. Solid evidence on SHS exposure is available only for healthy controls. An integrated approach with a combination of these markers still needs evaluation.

Download Full-text

Activation of gene expression by adenovirus and herpesvirus regulatory genes acting in trans and by a cis-acting adenovirus enhancer element

Cell ◽

10.1016/0092-8674(83)90215-5 ◽

1983 ◽

Vol 35 (1) ◽

pp. 127-136 ◽

Cited By ~ 78

Author(s):

Michael J. Imperiale ◽

Lawrence T. Feldman ◽

Joseph R. Nevins

Keyword(s):

Gene Expression ◽

Regulatory Genes ◽

Enhancer Element ◽

Cis Acting ◽

In Trans

Download Full-text

Current Practices for Reference Gene Selection in RT-qPCR of Aspergillus: Outlook and Recommendations for the Future

Genes ◽

10.3390/genes12070960 ◽

2021 ◽

Vol 12 (7) ◽

pp. 960

Author(s):

Meagan Archer ◽

Jianping Xu

Keyword(s):

Gene Expression ◽

Reference Gene ◽

Reference Genes ◽

Gene Selection ◽

Quantitative Polymerase Chain Reaction ◽

Specific Method ◽

Experimental Conditions ◽

Reference Gene Selection ◽

Physiological Processes ◽

The Stability

Aspergillus is a genus of filamentous fungi with vast geographic and ecological distributions. Species within this genus are clinically, agriculturally and biotechnologically relevant, leading to increasing interest in elucidating gene expression dynamics of key metabolic and physiological processes. Reverse-transcription quantitative Polymerase Chain Reaction (RT-qPCR) is a sensitive and specific method of quantifying gene expression. A crucial step for comparing RT-qPCR results between strains and experimental conditions is normalisation to experimentally validated reference gene(s). In this review, we provide a critical analysis of current reference gene selection and validation practices for RT-qPCR gene expression analyses of Aspergillus. Of 90 primary research articles obtained through our PubMed query, 17 experimentally validated the reference gene(s) used. Twenty reference genes were used across the 90 studies, with beta-tubulin being the most used reference gene, followed by actin, 18S rRNA and glyceraldehyde 3-phosphate dehydrogenase. Sixteen of the 90 studies used multiple reference genes for normalisation. Failing to experimentally validate the stability of reference genes can lead to conflicting results, as was the case for four studies. Overall, our review highlights the need to experimentally validate reference genes in RT-qPCR studies of Aspergillus.

Download Full-text